[A Case of T4 Esophageal Cancer with Refractory Chylothorax Developed Postoperatively].

A 65-year-old man was diagnosed as having middle thoracic esophageal cancer(c-T3N2M0, stage III ), and neoadjuvant chemoradiotherapy was performed.We performed surgical therapy.However, tumor and #113 lymph node invasion into the aortic arch was observed; therefore, it was judged that curative resection was difficult, and R2 surgery was performed instead. Postoperative diagnosis was Mt, CRT-type 5b, s-T4(aortic arch)N4(#113)M0, stage IV a.After surgery, pleural effusion was abundant and was diagnosed as chylothorax.Even though intestinal rest and octreotide administration were performed as a conservative treatment, chylothorax was not improved.Therefore, thoracoscopic thoracic duct ligation was performed on 8POD.After that, pleural effusion was still sustained, and pleural adhesions were performed.However, it did not prove to be effective.Furthermore, when Lipiodol lymphangiography was performed to identify the leakage site, the leakage of contrast medium was observed from the remaining lymph node.After lymphangiography twice(in total), pleural effusion disappeared, and the patient was discharged on the 75POD.In this case, we report an example in which lymph leakage disappeared due to lymphangiography for diagnostic purpose, while no improvement was observed in the lymphatic leakage from the remaining metastatic lymph node in T4 esophageal cancer with R2 surgery, nor with some treatments for chylothorax, including thoracic duct ligation.

Surveillance of short-segment Barrett's esophagus using ultrathin transnasal endoscopy.

BACKGROUND AND AIM: Newly developed ultrathin transnasal endoscope, the GIF-XP290N, makes possible a resolving power similar to the GIF-H260 at a distance of 3 mm. We conducted surveillance of subjects with Barrett's esophagus using this ultrathin transnasal endoscopy. In Japan the lower margin of the lower esophageal palisade vessels is defined the gastroesophageal junction in deep inspiration. We diagnose Barrett's esophagus if columnar epithelium is present on the oral side of the gastroesophageal junction. METHODS AND RESULTS: Barrett's esophagus was confirmed in 116 out of 135 subjects (85.9%), with 17 cases of short-segment Barrett's esophagus (SSBE) and 99 of ultra-short-segment Barrett's esophagus. Close observation of the Barrett's esophagus mucosal structural pattern using narrow band imaging revealed 29 cases with an oval or round pattern, 29 with a long straight pattern, 47 with a villous pattern, 8 with a cerebriform pattern, and 6 with an irregular pattern according to Goda classification. Mucosal biopsies from all subjects with SSBE are examined. Histological examination revealed intestinal metaplasia in only eight subjects. We grouped the oval/round and long straight patterns as closed type, and the villous, cerebriform, and irregular patterns as open type. Analysis of the relationship between these mucosal patterns and background factors revealed a significant correlation between intestinal metaplasia and the open-type pattern. CONCLUSION: We consider this new ultrathin transnasal endoscopy to be a useful technique for surveillance of Barrett's esophagus, especially SSBE.

Evaluation of gastric cancer diagnosis using new ultrathin transnasal endoscopy with narrow-band imaging: preliminary study.

BACKGROUND AND AIM: The new developed ultrathin transnasal endoscope, the GIF-XP290N, makes possible a resolving power similar to the GIF-H260 at a distance of 3 mm. In this study, using the GIF-XP290N, we evaluated whether endoscopic diagnosis (discrimination between benign and malignant) of gastric lesions is possible using nonmagnified narrow-band imaging (NBI) endoscopy. METHODS: The subjects were 255 consecutive patients who underwent screening of the gastrointestinal tract using new ultrathin transnasal endoscopy. Their average age was 65.2 ± 11.4 years. The male-female ratio was 2.5:1. All cases were examined using conventional white-light imaging (WLI) and nonmagnified NBI. When a depressed lesion was detected in the stomach, it was examined using WLI, then NBI close examination (at about 3 mm). We observed the mucosal structure of the lesion using close visualization with NBI. Concerning mucosal structural changes, we looked for a clear demarcation line between the lesion and the surrounding mucosa, and loss, irregularity, or nonuniformity of the lesion mucosal microsurface pattern. RESULTS: A total of 52 depressed lesions were examined. The histological diagnosis was cancer for 8 lesions, and noncancer for 44 lesions. WLI examination yielded a sensitivity of 50.0% (4/8), specificity of 63.6% (28/44), and accuracy 61.5% (32/52). On the other hand, NBI close examination yielded a sensitivity of 87.5% (7/8), specificity of 93.2% (41/44), and accuracy of 92.3% (48/52), significantly higher. CONCLUSION: NBI close examination using ultrathin transnasal endoscopy enables mucosal diagnosis even without magnification and was considered to be an effective technique for improving endoscopic diagnosis.

Soluble interleukin-6 receptor is a serum biomarker for the response of esophageal carcinoma to neoadjuvant chemoradiotherapy.

Preoperative chemoradiotherapy has been shown to improve the outcome of patients with esophageal cancer, but because response to this therapy varies, it is desirable to identify in advance individuals who would be unlikely to benefit, in order to avoid unnecessary adverse drug effects. The serum profiles of 84 cytokines and related proteins were determined in 37 patients with esophageal squamous cell carcinoma who received identical neoadjuvant preoperative chemoradiotherapy regimens and underwent surgical resection. Histological response to this therapy was assessed in surgically resected specimens. The serum soluble interleukin-6 receptor (sIL6R) level was significantly higher in 30 patients who failed to achieve a histological complete response (P = 0.005). Multivariate analysis revealed that the increased level of sIL6R was one of several significant independent predictors of an unfavorable outcome (hazard ratio, 2.87; P = 0.017). The increased level of this cytokine in patients who did not obtain a complete response was reproducibly observed in an independent cohort of 34 patients. Esophageal squamous cell carcinoma patients with an increased serum level of sIL6R are predicted to respond poorly to preoperative chemoradiotherapy, therefore, their exclusion from this treatment may be considered. Persistent systemic inflammation is implicated as a possible mechanism of resistance to this therapy.

[The efficacy of neoadjuvant chemotherapy with S-1/CDDP (SP) to the patients with large type 3 and type 4 gastric cancer].

Here, I examined the efficacy of neoadjuvant chemotherapy( NAC) with S-1/CDDP( SP) in my hospital. The subjects were 8 patients with advanced gastric cancer who had undergone NAC since 2007 (7 men and 1 woman; median age, 70 years). The staging before the treatment was Stage II A: 1 patient, II B: 2 patients, III B: 3 patients, III C: 1 patient, and IV: 1 patient. The macroscopic type of 3 and 5 patients was large type 3 and type 4, respectively. Gastrectomy was performed following the NAC with SP. The NAC response rate was 62.5%. In the histological response criteria, 1 patient was grade 0, 2 patients were grade 1a, 2 patients were grade 1b, and 3 patients were grade 2. Adverse events following the NAC were in the acceptable range. We noted that the presence of Stage IV or grade 0 histological response criteria to NAC indicated poor prognosis. Thus, I believe that preoperative surgery after NAC in Stage III gastric cancer should be considered to be curative.

[A case that showed an improved quality of life for rectal gastrointestinal stromal tumor patient treated with cytoreductive surgery].

A 49-year-old man was admitted to another hospital with the complaint of difficulty in defecating. He underwent laparotomy, and investigation of the biopsy revealed a huge intraperitoneal tumor. He began to take imatinib in April 2008 following a diagnosis of gastrointestinal stromal tumor (GIST), but the tumor increased in size. He was referred to our hospital for oral administration of sunitinib to reduce the tumor size. The tumor was 30 cm in diameter, and there were several peritoneal metastases around the liver. He began to take sunitinib in February 2009. The tumor increased in size from August 2010 but a partial remission was noted. We performed cytoreductive surgery in April 2011 as palliative care, but the tumor size increased again in October. We performed cytoreductive surgery again, but he died in December 2011. Although cytoreductive surgery for GIST is a potential treatment option, we suggest supportive care.

[A case of liver metastases from gastric cancer treated with stereotactic body radiation therapy].

A 69-year-old man underwent distal gastrectomy in September 2007 for type 2 gastric cancer with liver metastasis (S5) in LM area (p-T2N3aM1, Stage IV). After the operation, we performed chemotherapy. But the liver metastasis was enlarged, so we performed a partial hepatectomy in July 2008. After hepatectomy, liver metastases appeared on S6 and S7 in February 2009. So we performed the fifth-line chemotherapy with paclitaxel. The effect of paclitaxel was not so good. Therefore, SBRT was performed for the liver metastases (S6/7 and S7) in December 2009 and February 2010. After SBRT, he had no recurrent tumor. SBRT was one of the effective treatments for liver metastases from gastric cancer.

[A long-term survival case of hepatic metastases after curative gastrectomy by combined therapies].

A 74-year-old female was performed distal gastrectomy (f-T3N0H0P0CY0M0, Stage II) for gastric cancer in 2003. After 14 months, CT scan showed a metastasis in S7 segment of the liver. We performed chemotherapies until seventh-line and radio-frequency ablation (RFA). It finally got a long-term survival of 36 months postoperatively. RFA may be one of the useful therapies of liver metastasis from gastric cancer.

[A case report of long-term survival of advanced gastric cancer (P1CY1) after gastrectomy].

A-57-year-old male was performed a total gastrectomy (f-T3N2H0P1CY1M0, Stage IV) for gastric cancer in 2004. We kept performing chemotherapies until the seventh-line, and the patient at last had a long-term survival of 46 months after surgery. If we recognized a tumor that had a tendency to be progressive, the long-term survival may be obtained by changing a regimen as early as possible.

[A case of stenosis of the reconstructed jejunum due to recurrent cancer after total gastrectomy in which stent-in-stent placement was effective].

OBJECTIVES: We report one case of stenosis of the reconstructed jejunum due to recurrent cancer after total gastrectomy in which stenting was effective and good QOL was achieved. CASE: The patient was a 70-year-old woman. In July 2000, the patient underwent total gastrectomy.Roux-en Y reconstruction with a diagnosis of gastric cancer. The pathological diagnosis was U-Post, Type 3, por 1, T3, N1, H0, P0, CY0, M0, and Stage IIIA. From 9 months after the operation, aphagia occurred and stenosis of the reconstructed jejunum was noted. Based on a biopsy of the stenosis, a diagnosis of post-operative recurrent gastric cancer was made. Although the patient received two cycles of low-dose FP therapy, complete response was not obtained, and the patient stayed at home under the IVH control for about 4 months. In June 2001, the patient was hospitalized for a stent placement due to the patient's request. METHOD: After a guide wire was endoscopically inserted and a good passage on the anal side of the stenosis was confirmed, a stent was placed. Self Expandable Metallic Stent (SEMS) was used. CLINICAL COURSE: Following the stent placement, the patient was able to ingest orally, but 6.5 months later, stenotic symptoms developed and another stent was deployed (stent in stent). CONCLUSION: Stenting is relatively simple and less invasive, which is useful for the improvement of QOL and in recurrent cases as well.

Usefulness of serum protein profiling for prediction of preoperative chemoradiosensitivity of esophageal cancer.

We examined whether serum protein profiling is a reliable index for prediction of therapeutic efficacy of preoperative chemoradiotherapy (PCRT) in advanced esophageal cancer compared with evaluation of the efficacy of conventional clinical examination. We entered 42 patients who received PCRT and surgery between 1998 and 2002 into this study. Serum protein profiling was performed using the preoperative serum of the patient to select the marker set that enabled the efficacy of PCRT to be evaluated accurately. The efficacy of PCRT was predicted with the marker set, and the sensitivity, specificity and accuracy of the method were calculated based on evaluation of the efficacy by pathological examination. Similarly, therapeutic efficacy was also predicted based on evaluation of the efficacy of conventional clinical examination, and the results were compared with those of prediction by serum protein profiling. The correlation between each predictive examination and outcome was evaluated. The sensitivity, specificity and accuracy of prediction of therapeutic efficacy of PCRT by serum protein profiling were 90.9, 100 and 93.3%, respectively. In clinical examination, prediction of the efficacy of PCRT by three methods was as follows: by esophagography, sensitivity 76.0%, specificity 17.6%, accuracy 52.4%; by endoscopy, sensitivity 80.0%, specificity 11.8%, accuracy 52.4%; by computed tomography, sensitivity 60.0%, specificity 47.1%, accuracy 54.8%, respectively. These results demonstrated the superiority of serum protein profiling in predicting the therapeutic efficacy of PCRT compared with conventional clinical examination. Moreover, serum protein profiling was the only significant prognostic factor as regards the correlation with outcome by multivariate analysis.

[Long survival and effective treatment of unresectable gastric cancer by TS-1 based chemotherapy with a sequential combination].

We report a case of peritoneal cancer dissemination and cytological appearance of cancer cells with Type 4 gastric cancer. Treatment with unichemotherapy and combination chemotherapy with TS-1 proved successful. The patient was a 58-year-old female,who complained of abdominal pain. She was diagnosed as unresectable Type 4 gastric cancer, T 3 NxH 0 P 1 CY 1 M 0, Stage IV (cytology: Class V). Thirteen days after surgery, chemotherapy with TS-1 (80 mg/body/day, 4 weeks) at 2-week intervals in 1 course was performed. However, due to side effects with marrow restraint of grade 1, we changed to the following chemotherapy regimen: TS-1 (80 mg/body/day, 2 weeks) at 4-week intervals as 1 course (23 courses in total). After 16 courses, a partial response (PR) was noted. As additional therapy to recover tumor marker (CA19-9) after 21 courses, combination chemotherapy with TS-1 (80 mg/body/day, 2 weeks) and CDDP (25 mg/body/day, day 1, 8, 15 drip infusion) was performed as one course. This chemotherapy was then performed in 3 courses and tumor markers did not deteriorate, so we changed docetaxel (DOC) (50 mg/body/day(day 1)) to CDDP, and tumor markers returned to the normal value. No recurrence and no side effects appeared (hematological or non-hematological) during this combination chemotherapy.

[A long-term survival case of metachronous liver metastasis from gastric cancer].

A 62-year-old man was admitted for gastric cancer. He was performed a distal gastrectomy with Billroth I reconstruction in August 1999. Then he had remnant gastric cancer and metachronous liver cancer in November 2002. He was performed a total gastrectomy and partial hepatic resection. The histological findings of remnant stomach and liver cancer showed a same pattern of the primary gastric cancer. Another metachronous liver cancer appeared in March 2006. He was treated with chemotherapy using S-1 (day 1-21) and CDDP 20 mg/m2 (day 1, 8 and 15) q5w. The size of liver metastasis was kept the same for 16 months.

[Bone metastasis of gastric cancer].

We evaluated 19 patients with bone metastasis after surgery for gastric cancer. In a number of cases, the located in the tumor was U and M region, of macroscopic 3, and the histological type was poorly-differentiated adenocarcinoma with high-grade of lymphatic invasion. The major symptom was lumbago and back pain. The serum AFP level was high in 73.7% of the cases, and LDH was high in 47.7%. The metastatic lesion was predominantly seen in the bone with red pulp such as lumbar and thoracic vertebra and rib. The median survival time was 189 days (range: 24-509) with a poor prognosis. However, newly developed anticancer drugs were very effective for some cases, indicating that such chemotherapy should be tried for cases with bone metastasis.

[The efficacy of gastrojejunostomy for patients with unresectable gastric cancer].

We evaluated the efficacy of gastrojejunostomy for patients with unresectable gastric cancer. Thirteen patients had undergone gastrojejunostomy (GJ group) and 14 patients who couldn't receive gastrojejunostomy, but had only been observed into their abdomen in the operation (S group). Between two groups, there were no significant differences in the effective rate, median survival time and the number of dates the patient stayed home after the operation. Gastrojejunostomy was useful for patients with a strong case of stenosis in the stomach, and may improve the quality of life as one of the multimodal therapy.

Phase I Study of Docetaxel, Cisplatin, and 5-Fluorouracil Chemoradiotherapy for Local or Metastatic Esophageal Cancer.

BACKGROUND/AIM: Chemoradiotherapy outcomes for unresectable esophageal cancer remain poor. We designed a phase I study of docetaxel, cisplatin (CDDP), and 5-fluorouracil (5-FU) chemoradiotherapy. PATIENTS AND METHODS: Patients with T4 or M1 esophageal squamous cell carcinoma were enrolled. They received 2 chemotherapy cycles every 4 weeks with these initial doses (Phase I): docetaxel and CDDP (50 mg/m(2), days 1 and 29) with continuous 5-FU infusion (600 mg/m(2)/day, days 1-5 and 29-33). Concurrent radiotherapy (60 Gy) was initiated on day 1. Docetaxel and CDDP plus 5-FU doses were increased to 60 mg/m(2) plus 800 mg/m(2)/day. RESULTS: Out of the 15 patients enrolled, 13 completed the treatment. The MTDs were as follows: docetaxel (60 mg/m(2)), CDDP (60 mg/m(2)), and 5-FU (800 mg/m(2)/day). The overall response rate was 73%, with 27% achieving complete responses. CONCLUSION: In this phase I trial, docetaxel (60 mg/m(2)), CDDP (60 mg/m(2)), and 5-FU (600 mg/m(2)/day) were considered as the tolerable and active doses. These are the recommended doses for a future phase II trial.

Biliary obstruction reduces hepatic killing and phagocytic clearance of circulating microorganisms in rats.

Septic complications are common in patients with biliary obstruction. This is thought to be related, in part, to dysfunction of the hepatic reticuloendothelial system (RES). It has been reported that nearly 80% of circulating microorganisms are phagocytosed and killed within the liver and that clearance of circulating pathogens is significantly impaired in patients with jaundice. However, the effect of biliary obstruction specifically on phagocytic killing within the liver is less well described. Therefore this study was designed to quantify the effect of biliary obstruction, simultaneously and discriminately, on two important components of hepatic RES function (phagocytosis and phagocytic killing). Rats were divided into three experimental groups: control, sham, and jaundiced (common bile duct ligation). At 7, 10, 14, and 21 days after operation, E. coli labeled with both 125I and 51Cr were injected intravenously. Using the previously validated double-labeled in vivo E. coli technique, hepatic phagocytic clearance (HPC), hepatic killing efficiency (HKE), and net hepatic killing (NHK) were measured. Common bile duct ligation resulted in a significant decrease in the HPC of E. coli 10, 14, and 21 days postoperatively. Similarly, HKE was significantly decreased in jaundiced animals by postoperative day 10, but returned to baseline values by day 14. The net effect of these changes in HPC and HKE values were reflected in a significant reduction in NHK in jaundiced animals. Results of the present study suggest that obstructive jaundice impairs both phagocytosis and phagocytic killing within the liver. These findings may help to explain the susceptibility of patients with biliary tract obstruction to the morbidity and mortality of septic complications.

Concurrent preoperative chemoradiotherapy for stage III or IV esophageal squamous carcinoma.

The poor progress of advanced esophageal carcinoma cannot be expected to be improved by surgical treatment alone. We retrospectively examined the results of surgery alone (SA: 39 cases) and of concurrent preoperative chemoradiation therapy (PCRT: 51 cases) for stage III or IV esophageal squamous carcinoma. In the PCRT group, the rate of pathological complete response was 31.4% for the primary lesion and 31.1% for metastatic lymph nodes, which viable cancer cells were not recognized in either region in 25.5% of all cases. In the PCRT group, grade 2 or more toxicity was found in 39 cases of leukopenia, 10 cases of anemia, 7 cases of thrombocytopenia, 11 cases of esophagitis, 4 cases of stomatitis, 2 cases of nausea, 2 cases of diarrhea, 2 cases of liver disfunction and 2 cases of infection. In 2 cases, PCRT was terminated for about 3 weeks because of thrombocytopenia. In the remaining 49 cases, PCRT was administered as scheduled. No statistically significant differences were noted between the PCRT group and the SA group in postoperative complications. There was postoperative recurrence in 16 cases (31.4%) in the PCRT group and 26 cases (66.7%) in the SA group (p=0.008). In stage III, the 5-year survival rate was 58.6% for the PCRT group and 17.2% for the SA group (p=0.022). In stage IV, the survival rate was 0% for the SA group and 16.7% for the PCRT group, showing better results in the latter, although there was no statistically significant difference. Multivariate analysis of prognostic variables revealed that therapeutic method (presence or absence of PCRT) contributed the greatest to the prognosis. These results indicate that PCRT is an effective adjuvant therapy for squamous cell carcinoma.

Tumor response after low-dose preoperative radiotherapy combined with chemotherapy for squamous cell esophageal carcinoma.

AIM: Patients with T3 or more squamous cell esophageal cancer underwent low-dose preoperative radiotherapy with chemotherapy, to reduce local recurrence, followed by surgery. The aim was to ascertain tumor response and assess prognostic factors. PATIENTS AND METHODS: Between May 2002 and June 2011, 37 consecutive patients with esophageal cancer underwent chemoradiotherapy followed by surgery. The numbers of patients in clinical stages IIA/IIIA/IIIB/IIIC were 2/24/7/4, respectively. All were given a dose of 30 Gy in 15 fractions, with concurrent chemotherapy using cisplatin and fluorouracil. Curative surgery was performed a median of 1.2 months after completion of chemoradiotherapy. RESULTS: Based on the findings from surgery, 26 patients (70%) achieved a stage reduction and six patients (16%) had a complete pathological response. The numbers of patients undergoing resections microscopically complete, with microscopically positive margins, and macroscopically positive margins were 33, 3, and 1, respectively. During a median follow-up period of 22.5 months, the two-year progression-free survival and overall survival were 62.1% [95% confidence interval (CI)=45.8 to 78.4%] and 71.9% [95% CI=55.1 to 88.7%], respectively. Statistically significant prognostic factors for overall survival were age [hazard ratio=6.6; 95% CI=1.1 to 38; p=0.04] and pathological T factor [hazard ratio=10.2; 95% CI=1.4 to 77; p=0.02]. No patients died as a result of surgery. CONCLUSION: Seventy percent of patients with esophageal cancer who received radiotherapy dose of 30 Gy in 15 fractions combined with chemotherapy achieved a stage reduction with low toxicity.

Phase II study of combined chemotherapy with docetaxel, CDDP and 5-FU for highly advanced esophageal cancer.

Advanced esophageal cancer with widespread metastasis to lymph nodes or other organs is difficult to treat and has an extremely poor prognosis. A new combined chemotherapy of docetaxel with cisplatin (CDDP) and 5-fluorouracil (5-FU) (DPF therapy) was performed and its efficacy and safety were examined. Among those hospitalized between May 2003 and October 2009, 30 patients with stage III or stage IV unresectable, untreated advanced esophageal squamous cell carcinoma which had invaded other organs were enrolled in this study. The regimen of DPF therapy was as follows: a set of intravenous drips of 60 mg/m(2) of docetaxel (day 1), 60 mg/m(2) of CDDP (day 1) and 800 mg/m(2) of 5-FU (days 1-5) was administered twice at an interval of 3 to 4 weeks. Antitumor effects, adverse reactions and treatment outcomes were then examined. The patients included 26 men and 4 women aged 40 to 73 years (average age, 58.1 years), and the performance status (PS) was 1 in 18 cases and 2 in 12 cases. The main location of the esophageal cancer was the upper/middle/lower thoracic esophagus in 7/14/9 cases, respectively. Clinical stage was III in 5 cases and IV in 25. The effective rate of DPF therapy was 83.3% for the primary lesion (complete response, CR: 4 cases, partial response, PR: 21 cases), 72.4% for lymph node metastasis (CR: 3 cases, PR: 18 cases) and 72.0% for distant organ metastasis (CR: 3 cases, PR: 15 cases). The observed adverse reactions of grade 2 or higher of National Cancer Institute-Common Toxicity Criteria (NCI-CTC) included anemia (16.7%), leukopenia (73.3%), liver dysfunction (20.0%), anorexia (16.7%), stomatitis (33.3%), esophagitis (16.7%), alopecia (16.7%) and diarrhea (26.7%). The therapy completion rate was 96.7% and the therapy-related death rate was 3.3%. Treatments given after the completion of the DPF therapy were surgery in 6 cases, chemotherapy such as additional DPF in 12, chemoradiation in 4, esophageal stent placement in 1, and no treatment in 7. The patients' median survival time was 271 days, the 1-year survival rate was 41.9% and the 5-year survival rate was 13.3%. DPF therapy can be used as a standard chemotherapy for advanced esophageal cancer in view of its strong antitumor effect and relatively safe outcome.