Current treatment strategies and future perspectives for gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that originate from the gastrointestinal tract, mostly from the stomach. GISTs are derived from the myenteric interstitial cells of Cajal and are caused by several mutations in the c-kit and platelet-derived growth factor receptor genes. Clinically, GISTs are detected by endoscopic and imaging findings and are diagnosed by immunostaining. Surgery is the first line of treatment, and if the tumor is relatively small, minimally invasive surgery such as laparoscopy is performed. In recent years, neoadjuvant therapy has been administered to patients with GISTs that are suspected of having a large size or infiltration to other organs. Postoperative adjuvant imatinib is the standard therapy for high-risk GISTs. It is important to assess the risk of recurrence after GIST resection. However, the effect of tyrosine kinase inhibitor use will vary by the mutation of c-kit genes and the site of mutation. Furthermore, information regarding gene mutation is indispensable when considering the treatment policy for recurrent GISTs. This article reviews the clinicopathological characteristics of GISTs along with the minimally invasive and multidisciplinary treatment options available for these tumors. The future perspectives for diagnostic and treatment approaches for these tumors have also been discussed.

Solitary peritoneal metastasis of gastrointestinal stromal tumor: A case report.

BACKGROUND: A gastrointestinal stromal tumor (GIST) is a mesenchymal tumor of the gastrointestinal tract that is most commonly found in the stomach. Recurrence of GISTs mostly occurs in the liver or peritoneum, and in most cases, multiple metastases occur. As a solitary peritoneal metastasis is rare, an appropriate treatment strategy has not been established. Here, we report a case of solitary peritoneal metastasis after complete resection of gastric GIST. CASE SUMMARY: A 76-year-old woman was diagnosed with stomach GIST and underwent laparoscopic local resection using the CLEAN-NET method. As the recurrence risk was intermediate, adjuvant imatinib therapy was not administered. Two years after surgery, routine computed tomography revealed an abdominal mass between the dorsal side of the right hepatic lobe and right kidney. Other imaging tests did not reveal any abnormalities. Laparoscopic observation showed that the tumor was located at the retroperitoneum, and intraperitoneal dissemination was not found. Therefore, we performed laparoscopic tumor resection. Immunohistochemically, the tumor was positive for c-kit and CD34 and had a relatively high mitotic index and MIB-1 Labeling index. We administered adjuvant imatinib therapy. There was no evidence of recurrence 3 years after the operation. CONCLUSION: This is the first reported case of a solitary recurrence of GIST in the peritoneum treated with complete laparoscopic resection.

[Surgical Resection and Adjuvant Chemotherapy with FOLFOX6 for Primary Duodenal Adenocarcinoma and Nodal Metastasis Resulted in Complete Remission].

Primary duodenal adenocarcinoma is a rare disease, and cases with nodal metastases have a poor prognosis. A 46-year-old man complaining of bloody stool visited our hospital. Endoscopy, CT, and PET-CT showed adenocarcinoma in the 2nd portion of the duodenum. We performed radical resection (PpPD) and pathological findings showed T3N1M0 (Stage III). Chemotherapy consisting of FOLFOX6 was administered for 6 months after surgery. The patient was alive without recurrence 5 years later. This case suggests that adjuvant chemotherapy (FOLFOX regimen) following curative resection including lymph node removal is an effective treatment for cases with tumor involvement of the lymph nodes.

[A case of an advanced gastric cancer patient on hemodialysis achieving long-term progression-free survival after CPT-11+CDDP therapy].

A 59-year-old male with chronic kidney disease was diagnosed as having advanced gastric cancer(cT2N1P0H1M0), and CPT-11+CDDP therapy was started for him simultaneously with hemodialysis(HD). Serum CDDP concentrations were measured in the 1st course, and free-platinum(f-Pt)showing the anti-tumor effect was found to be eliminated by HD. Serum f-Pt levels, however, re-elevated until 24 hours after HD completion. Serum concentrations measured in the 15th course showed that f-Pt levels became higher than those observed in the 1st course, suggesting that CDDP was not completely removed by HD. Medical treatment was continued until the liver metastases were judged to be a progression disease at completion of the 18th course. When CDDP was administered to patients on HD, it was necessary to pay attention to various CDDP serum concentrations, and to tailor the dose to a tolerable level in each patient. Such an individual therapy might enable CPT-11+CDDP therapy to be one of the medical treatments of choice for advanced gastric cancer patients on HD.

[A case of synchronous multiple liver metastasis of sigmoid colon cancer with a pathological complete response to combination chemotherapy of 5-FU/LV and bevacizumab].

A 73-year-old man was referred to our hospital with sigmoid colon cancer in July 2009. CT and MRI showed synchronous multiple liver metastasis. After a sigmoid colon resection in August, he received convergent chemotherapy in combination with 5-fluorouracil(5-FU)/Leucovorin(LV)(RPMI regimen)and bevacizumab for liver metastasis. After two courses without any major adverse effects, liver metastasis remarkably reduced on CT and MRI examination. We thus performed a liver resection, and pathological examination revealed a complete response in liver. Combination chemotherapy of 5-FU/LV and bevacizumab can be expected to provide safe and effective treatment for liver metastasis of colon cancer.

[A case of liver metastases from rectal cancer showed a complete response by FOLFIRI and bevacizumab chemotherapy].

A 62-year-old man had undergone anterior resection of rectum for rectosigmoid colon cancer with liver metastases. Postoperatively, the FOLOFOX6 regimen was performed in three courses. Metastatic liver tumors showed progressive disease(PD) on CT scan. The treatment was then changed to the FOLFIRI regimen for three courses. Metastatic liver tumors showed a partial response(PR)on CT scan. After six courses of the FOLFIRI regimen, the patient was given seven courses of the FOLFIRI +BV regimen. Hepatic resection of S2, S3, S4 and S6 segment was performed. The histological effect of chemotherapy was complete response(CR).

Bacterial translocation: not a clinically relevant phenomenon in colorectal cancer.

The aim of this study was to identify the risk factors for bacterial translocation and to determine the clinical significance of bacterial translocation in patients with colorectal cancer. Mesenteric lymph node sampling was performed to identify the presence of bacterial translocation in 75 patients with colorectal cancer undergoing laparotomy. Bacterial translocation was identified in 29 patients (39%), with the most common organism being Escherichia coli (31%). Three factors for bacterial translocation were identified, including a preoperative low peripheral lymphocyte count, metastasis to lymph nodes, and invasion depth (= T3). Stepwise regression analysis, however, selected only = T3 [odds ratio (OR) 4.0, 95% confidence interval (CI) 1.2-13.5]. Altogether, 35% of patients with bacterial translocation developed septic complications, compared with 20% in patients without bacterial translocation. In the multivariate analysis, bacterial translocation was not an independent risk factor for infection, with an OR of 1.8 (95% CI 0.56-5.96). Systemic inflammatory response syndrome developed on the first day in 62% of patients with bacterial translocation, compared with 50% of patients without bacterial translocation. Adjusting for the other factors, bacterial translocation was not a significant risk factor in the occurrence of systemic inflammatory response syndrome after surgery (OR 1.1, 95% CI 0.37-3.29). We concluded that in patients with colorectal cancers bacterial translocation does occur and is increased in patients with deep invasion. However, it appears to be of no clinical significance.

Combined assessment of beta-D-glucan and degree of candida colonization before starting empiric therapy for candidiasis in surgical patients.

The purpose of the study was to investigate whether examination for plasma beta-D-glucan, a cell wall constituent of fungi, is useful for selecting surgical patients with Candida colonization who would benefit from empiric antifungal therapy. We administered fluconazole to postoperative patients with Candida colonization who have risk factors for candidemia and complained of persistent fever despite prolonged antibacterial therapy. We then analyzed the clinical outcomes regarding the number of sites colonized with Candida spp. and plasma beta-D-glucan. Of the 32 patients positive for alpha-D-glucan, 15 (46.9%) responded to the empiric therapy; only 9% of those who were negative responded (p < 0.01). In the multiple logistic regression analysis, being positive for alpha-D-glucan was a significant factor predicting response, with an adjusted odds ratio of 12.9 in patients with Candida colonization [95% confidence interval (CI) 2.07-80.73) (p < 0.01). In addition, the number of sites colonized with Candida spp. was a significant factor predicting response, with an estimated exposure odds ratio of 7.57 for those who were colonized at three or more sites compared with those colonized at one site (95% CI 1.20-47.70) (p = 0.031). In patients with Candida colonization, assessment of beta-D-glucan was useful for deciding whether to start empiric therapy for suspected candidiasis in surgical patients.