[A 3mm Gastric Neuroendocrine Tumor That Metastasized to a Lymph Node].

A 46-year-old man underwent a medical check-up and gastrointestinal endoscopy, which revealed a brown lesion at the greater curvature of the gastric body. Biopsy was performed, and a gastric neuroendocrine tumor(NET)was diagnosed. The serum levels of gastrin and other tumor markers were not elevated. The preoperative diagnosis was Rindi type Ⅲ gastric NET, and laparoscopic distal gastrectomy with D1 plus lymph node dissection was performed. Histological examination showed that the resected specimen was positive for chromogranin A, CD56, and synaptophysin, which was consistent with the findings of NET. Even though the tumor diameter was only 3 mm, a metastatic #4d lymph node was found. This case suggests that Rindi type Ⅲ gastric NET has high malignant potential, and gastrectomy with lymph node dissection is necessary, regardless of tumor size.

[A Case of Appendiceal Adenocarcinoma with Vesico-Appendiceal Fistula Treated by Additional Laparoscopic Excision].

A 40-year-old woman was admitted to our hospital with the chief complaint of miction pain. MRI showed fundal wall thickening of the bladder in contact with the appendix. Under cystoscopy, redness of the mucous membrane was found in the posterior wall of the bladder. Therefore, laparo-appendectomy with partial cystectomy was performed. Microscopically, adenocarcinoma cells were observed in the lumen of the appendix, invading the wall of the urinary bladder at the fundus of the appendix. We performed laparo-ileocecal resection for a regional lymphadenectomy. Thus, the patient was diagnosed with adenocarcinoma of the appendix[V, type 3, 16×7 mm, tub2, pT4b(SI, urinary bladder), int, INF b, ly0, v0, pN0, cM0, pStage Ⅱ]. The patient has been receiving adjuvant chemotherapy using capecitabine for 6 months. There was no evidence of recurrence after 9 months of follow-up.

[Multidisciplinary Therapy for Advanced Gastric Cancer with Liver and Brain Metastases].

A 68-year-old man was admitted to our hospital. He was diagnosed with advanced gastric cancer with multiple liver metastases. The primary tumor was treated with distal gastrectomy with D2 dissection and anti-cancer agents, and then he was scheduled for a 2-stage hepatic resection. After surgery, the liver metastases disappeared, and he was diagnosed with a CR. However he complained of dizziness and was diagnosed with metachronous brain matastasis. Multidisciplinary treatment including resection and radiotherapy was administerd and he survived for 5 years after diagnosis.

[A Case of Laparoscopic Gastrectomy in a Patient with Refractory Vasospastic Angina].

We report a case of laparoscopic gastrectomy in a patient with refractory vasospastic angina. An 83-year-old man received 2 types of oral coronary vasodilators but complained of chest pain about twice a week thereafter. He was diagnosed with refractory vasospastic angina. Upper gastrointestinal endoscopy was performed for tarry stools and revealed a type 2 tumor in the anglar posterior wall. CT revealed no lymph node swelling or metastasis. Laparoscopic gastrectomy was performed, and intravenous administration of coronary vasodilators was started before the operation. During the operation, coronary spasm could be prevented while being careful not to induce circulation change, bleeding, or traction of the peritoneum. Many cases of coronary spasm-related angina in the absence of a history of angina have been reported during non-cardiac operations. In such cases, careful coronary spasm is necessary.

[A Case of Cecal Cancer with Multiple Cutaneous Metastases].

We encountered a case of cutaneous metastases from colorectal carcinoma. A 63-year-old woman underwent laparoscopic-assisted ileocecal resection for cecal cancer. Computed tomography (CT) showed multiple liver metastases. The tumor was diagnosed as a well-differentiated adenocarcinoma and was staged as pSE, pN1, sH2, ly1, v1, CP0cM0, fStage Ⅳ. She was treated with 33 courses of the 5-fluorouracil, Leucovorin, and irinotecan (FOLFIRI) regimen and 15 courses of the 5-fluorouracil, Leucovorin, and oxaliplatin (mFOLFOX6) plus bevacizumab regimen. Thirty-four months after resection, multiple cutaneous tumors were noted, predominantly on the lower abdomen, and we resected 2 of them. Histologically, the specimens were diagnosed as well-differentiated adenocarcinoma, which was similar to that of cecal carcinoma. After 1 course of regorafenib, she died 3 years after the primary surgical resection.

[The usefulness of intraoperative Doppler echo and laparoscopic echo in laparoscopic colectomy].

Laparoscopic surgery has been increasingly performed in colon cancer patients; it has also been adapted for cases of advanced colorectal cancer. While performing an operation for rectosigmoid colon cancer, preservation of the left colic artery and prompt and accurate detection of the branch of the left colic artery from the inferior mesenteric artery is important. Detecting the left colon arterial bifurcation takes time, especially because of the presence of mesenteric fat, which is observed in many cases. In addition, in cases in which preoperative enhanced computed tomography (CT) cannot be performed, the surgery is sometimes performed without knowing the traveling vessel. As palpation is impossible, it is impossible to tactile running of the arteries as laparotomy in laparoscopic surgery. With endoscopic echo or Doppler echo, real-time identification of the blood vessels during surgery is possible without being invasive. It would be in laparoscopic surgery impossible palpation, and the combined use of intraoperative echo in ensuring the safety to be useful.

[A case of palliative resection resulting in improvement in quality of life in a patient with colon cancer and simultaneous ovarian metastasis].

A 72-year-old woman was admitted for investigation of lower abdominal bloating and melena. She was diagnosed with rectal cancer with ascites, multiple liver metastases, and large bilateral ovarian metastases. The patient underwent bilateral oophorectomy for the ovarian tumors and a Hartmann procedure for rectal cancer. The ovarian lesions were diagnosed as ovarian metastasis of colorectal cancer by histological analysis. Ascites and lower abdominal bloating resolved after the intervention. At 11 months after surgery, the patient is alive and well. Ovarian metastasis from colorectal cancer is relatively rare and associated with poor prognosis. Radical intervention is generally not possible in the presence of metastases, but in the present case, the ovarian tumors were large. It is often difficult to determine the optimal type of invasive surgery, although excision of the lesion may provide palliative relief. In this case, the patient's quality of life improved following palliative resection of the primary colon cancer and ovarian metastases.

Concurrent biological targeting therapy of squamous cell carcinoma of the esophagus with cetuximab and trastuzumab.

The ERBB proteins are cell membrane tyrosine kinase receptors. Among these receptors, ERBB1 (EGFR or HER1) and ERBB2 (HER2/Neu) have been reported to be the most important in terms of the development and progression of squamous cell carcinoma of the esophagus (SCC). Thus, targeting of ERBB1 and ERBB2 may become a promising strategy to treat SCC. In the present study, we examined ERBB1 and ERBB2 expression of SCC cell lines (TT, TE2, TE6 and TE10) and tumor samples. In addition, we evaluated the effect of the anti-ERBB1 antibody cetuximab and the anti-ERBB2 antibody trastuzumab for SCC in vitro and in vivo. Biological activities (receptor downregulation, the phosphorylation of MAPK and AKT) induced by the two agents were also investigated. Immunohistochemistry of SCC samples showed that ERBB1 was detected in 84%, while ERBB2 was detected in 30%. RT-PCR analysis revealed that ERBB1 and ERBB2 mRNA were detectable in all four cell lines. MTT cell proliferation analysis showed that cetuximab, but not trastuzumab, inhibited growth in each of the SCC cell lines in a dose-dependent manner. Further, cetuximab and trastuzumab used together produced stronger inhibition of growth compared to cetuximab alone. Cetuximab downregulated ERBB1, but not ERBB2, at the TE6 cell surface. However, neither ERBB1 nor ERBB2 showed any downregulation by trastuzumab at the TE6 cell surface. Cetuximab, not but trastuzumab, inhibited the phosphorylation of MAPK and Akt. When administered in combination, the two agents inhibited Akt phosphorylation to a greater degree compared to treatment with cetuximab alone. In the in vivo study, cetuximab, but not trastuzumab, significantly inhibited the TT tumors. Additionally, the combination of cetuximab with trastuzumab induced a synergistic inhibitory antitumor effect in the TT tumors. In conclusion, combination of cetuximab and trastuzumab revealed a synergistic antitumor effect for SCC in vitro and in vivo. The antitumor effect may be induced by the inhibition of the phosphorylation of Akt. These findings suggest that combination therapy including cetuximab and trastuzumab may be a promising strategy to treat SCC.

Laparoscopic resection of ileal lipoma diagnosed by multidetector-row computed tomography.

Intussusception is rare in adults and it is difficult to diagnose on admission. We present the case of a 43-year-old woman with the chief complaint of nausea and upper abdominal pain. Abdominal multidetector-row computed tomography showed ileo-ileal small bowel intussusception with an intraluminal soft tissue mass with attenuation numbers suggestive of a lipoma. The patient was treated with a laparoscopic-assisted extracorporeal partial resection of the small bowel including ileal lipoma, followed by a functional end-to-end anastomosis. Histologic diagnosis of the resected tumor, 2.4×2.0×2.0 cm, was an intestinal lipoma. This case serves as the basis of a review of small bowel intussusception in adults secondary to lipomas. It focuses on the utility of multidetector-row computed tomography and the cosmetic, physical, and economic benefits of laparoscopic surgery as well as the rarity of the disease.

Survival of geriatric patients after percutaneous endoscopic gastrostomy in Japan.

AIM: To examine the long term survival of geriatric patients treated with percutaneous endoscopic gastrostomy (PEG) in Japan. METHODS: We retrospectively included 46 Japanese community and tertiary hospitals to investigate 931 consecutive geriatric patients (≥ 65 years old) with swallowing difficulty and newly performed PEG between Jan 1st 2005 and Dec 31st 2008. We set death as an outcome and explored the associations among patient's characteristics at PEG using log-rank tests and Cox proportional hazard models. RESULTS: Nine hundred and thirty one patients were followed up for a median of 468 d. A total of 502 deaths were observed (mortality 53%). However, 99%, 95%, 88%, 75% and 66% of 931 patients survived more than 7, 30, 60 d, a half year and one year, respectively. In addition, 50% and 25% of the patients survived 753 and 1647 d, respectively. Eight deaths were considered as PEG-related, and were associated with lower serum albumin levels (P = 0.002). On the other hand, among 28 surviving patients (6.5%), PEG was removed. In a multivariate hazard model, older age [hazard ratio (HR), 1.02; 95% confidence interval (CI), 1.00-1.03; P = 0.009], higher C-reactive protein (HR, 1.04; 95% CI: 1.01-1.07; P = 0.005), and higher blood urea nitrogen (HR, 1.01; 95% CI: 1.00-1.02; P = 0.003) were significant poor prognostic factors, whereas higher albumin (HR, 0.67; 95% CI: 0.52-0.85; P = 0.001), female gender (HR, 0.60; 95% CI: 0.48-0.75; P < 0.001) and no previous history of ischemic heart disease (HR, 0.69; 95% CI: 0.54-0.88, P = 0.003) were markedly better prognostic factors. CONCLUSION: These results suggest that more than half of geriatric patients with PEG may survive longer than 2 years. The analysis elucidated prognostic factors.

[A case with multiple liver metastases of gastric cancer responding completely to S-1 therapy].

We experienced a case with multiple liver metastases of gastric cancer that disappeared by S-1 alone. The patient has survived without recurrence after the disappearance of liver metastases.

Efficacy of S-1 for gastric cancer patients with positive peritoneal lavage cytology.

BACKGROUND/AIMS: Positive peritoneal lavage cytology (PLC) is a strong predictor of subsequent frank peritoneal dissemination. The prognosis for patients with positive PLC is as poor as with macroscopic peritoneal dissemination. We examined the clinical efficacy of S-1 chemotherapy against gastric cancer with positive PLC after macroscopically curative resection. METHODOLOGY: Among our gastric cancer patients proving to have positive PLC after operation, 17 treated between 2000 and 2005 and 20 treated between 1986 and 1999 respectively represented S-1 and non-S-1 groups, between which we compared survival rates. S-1 was administered orally twice daily at a dose of 80 mg/m2/day for 28 consecutive days followed by a 14-day pause, thus repeating the cycle every 6 weeks. RESULTS: S-1 was administered for more than 2 cycles in all patients (median, 10 cycles). Grade 3 adverse reactions to S-1 occurred in two patients. Other adverse reactions were grade 2 or less. Cumulative survival in the S-1 group was better than in the non-S-1 group (p=0.0034), with 1- and 3-year survival rates of 87.5% and 71.6% vs. 59.0% and 17.1%. CONCLUSIONS: S-1 is effective as postoperative chemotherapy for gastric cancer patients with positive PLC after macroscopically curative resection.

[A case of cytology-positive, stage IV gastric cancer, alive with no recurrence for 4 years, curatively treated with combination chemotherapy using S-1, CPT-11 and subsequent total gastrectomy].

A 68-year-old man was admitted to another hospital because of progressive weight decrease and appetite loss. Endoscopic examination revealed type 4 advanced gastric cancer at the upper body of the stomach. In February, 2003, he patient had probe laparotomy because there was a small amount of ascites in his peritoneal cavity, and intraoperative washing cytology revealed cancer cells in ascites.Subsequently, we started chemotherapy using S-1 and CPT-11. S-1 at a dose of 100 mg/day was orally administered for 2 weeks, and CPT-11 at a dose of 90 mg/body was intravenously administered once a week for 2 weeks followed by a 2-week drug-free period as 1 course. After 7 courses of the chemotherapy, the main lesion endoscopically vanished.Subsequently, the patient underwent curative total gastrectomy together with D2 lymph node dissection. Intraoperative cytology revealed no cancer cells, and histological examination of the primary lesion showed cancer cells invading the subserosa with no metastasis to any dissected lymph nodes. This therapy induced Grade 2 effect on cancer cells.Postoperatively, only S-1 was administered to the patient, who has remained alive with no recurrence for 4 years as of January, 2007.

[Self-expandable metallic stent for palliation of unresectable esophagogastric malignancies].

While self-expandable metallic stents (EMS) have been reported to be useful for palliation of unresectable esophagogastric malignancies, complications accompanying such stenting also have been pointed out. Both advantages and disadvantages of EMS stenting are discussed on the basis of 25 cases of esophageal cancer and 5 cases of gastric cancer treated in our institute. Although dysphagia improved in 26 of the 30 patients with stenosis, only 14 of the patients who had been able to ingest more than 1,200 kcal of food could be discharged to their homes. Complications were noted in 12 (48%) of the esophageal cancer patients and 4 (80%) of the gastric cancer patients, including incomplete sealing of esophagorespiratory fistula in 6, tumor ingrown in 3, mucosal hyperplasia in 2, stent migration in 2 and reflux of digestive juice in 1. The patients with complications took food for shorter periods than those who had no complications. Successful patient outcomes can be achieved by the prevention of complications accompanying stenting and mastering the techniques to overcome those complications described above.

[A surgical case of recurrent gastric cancer successfully treated by TS-1 plus low-dose consecutive administration of CDDP following TS-1 monotherapy].

The patient was a 65-year-old woman who was discovered to have recurrent gastric cancer involving para-aortic lymph nodes 21 months after postoperative low-dose FP therapy for gastric cancer. The recurrent cancer was judged to be unresectable, and TS-1 chemotherapy (one course consisting of 4-week administration of 100 mg/day and a 2-week withdrawal period) was performed. Although a complete response occurred in the para-aortic lymph nodes and a partial response in the residual stomach (i.e., only a shallow erosion remained) after the end of course 2, histological examination showed "no change". The following regimen was therefore used in courses 3 and 4: 6-day administration of CDDP at a dose of 15 mg/body (10 mg/m2)/day the first week, concomitant administration of 90 mg/body (60 mg/m2) of CDDP plus 100 mg/day of TS-1 the next three weeks, and two-week withdrawal of chemotherapy. Since down-staging was observed at the completion of course 4, total gastrectomy of the residual stomach was performed. No noteworthy adverse reactions to chemotherapy were observed, and good patient QOL (e.g., appetite) was achieved. Based on these findings, this chemotherapy regimen appears to be an effective treatment modality for far advanced gastric cancer, particularly involving the abdominal para-aortic lymph nodes.