Search

Background Sphingosine-1-phosphate (S1P), a pleiotropic bioactive lipid mediator, has been implicated as a key regulatory molecule in cancer through its ability to promote cell proliferation, migration, angiogenesis, and lymphangiogenesis. Previous studies suggested that S1P produced by sphingosine kinase 1 (SphK1) in breast cancer plays important roles in progression of disease and metastasis. However, the associations between S1P and clinical parameters in human breast cancer have not been well investigated to date. Materials and methods We determined levels of S1P and other sphingolipids in breast cancer tissue by electrospray ionization-tandem mass spectrometry. Associations between S1P levels and clinicopathologic features of the tumors were analyzed. Expression of phospho-SphK1 (pSphK1) in breast cancer tissues was determined by immunohistochemical scoring. Results Levels of S1P in breast cancer tissues were significantly higher in patients with high white blood cell count in the blood than those patients without. S1P levels were lower in patients with human epidermal growth factor receptor 2 overexpression and/or amplification than those patients without. Furthermore, cancer tissues with high pSphK1 expression showed significantly higher levels of S1P than cancer tissues without. Finally, patients with lymph node metastasis showed significantly higher levels of S1P in tumor tissues than the patients with negative nodes. Conclusions To our knowledge, this is the first study to demonstrate that high expression of pSphK1 is associated with higher levels of S1P, which in turn is associated with lymphatic metastasis in breast cancer.

Background Sphingolipids, including sphingosine-1-phosphate (S1P) and ceramide, have emerged as key regulatory molecules that control various aspects of cell growth and proliferation in cancer. Although important roles of sphingolipids in breast cancer progression have been reported in experimental models, their roles in human patients have yet to be determined. The aims of this study were to determine the levels of sphingolipids including S1P, ceramides, and other sphingolipids, in breast cancer and normal breast tissue and to compare the difference in levels of each sphingolipid between the two tissues. Materials and methods Tumor and noncancerous breast tissue were obtained from 12 patients with breast cancer. Sphingolipids including S1P, ceramides, and their metabolites of sphingosine, sphingomyelin, and monohexosylceramide were measured by liquid chromatography–electrospray ionization–tandem mass spectrometry. Results The levels of S1P, ceramides, and other sphingolipids in the tumor were significantly higher than those in normal breast tissue. There was a relatively strong correlation in the levels of S1P between the tumor and those of normal breast tissue from the same person. On the other hand, there was no correlation in the levels of most of the ceramide species between the tumor and those of normal breast tissue from the same person. Conclusions To our knowledge, this is the first study to reveal that levels of sphingolipids in cancer tissue are generally higher than those of normal breast tissue in patients with breast cancer. The correlation of S1P levels in these tissues implicates the role of S1P in interaction between cancer and the tumor microenvironment.

A 71-year-old woman diagnosed with Fournier's gangrene caused by penetration of a rectal carcinoma was referred to our hospital. Emergency drainage and sigmoid colostomy were performed. Pathological examination of a biopsy sample showed moderately differentiated tubular adenocarcinoma. Abdominoperineal resection with bilateral salpingo-oophorectomy and hysterectomy was performed with curative intent after 4 courses of chemotherapy with S-1 and oxaliplatin. The postoperative pathological diagnosis was StageⅡ (pT4bN0M0). The patient received tegafur/uracil and Leucovorin as adjuvant chemotherapy. Seven months after the curative operation, partial pneumonectomy was performed for the recurrence of the rectal carcinoma in the right lung. Eight months after pneumonectomy, recurrent tumors were observed in the right lung and subcutaneous fat layer of the right buttock along the drainage site. The tumor in the right buttock was excised along with part of the gluteus maximus, and partial pneumonectomy was then performed. Three years and 6 months after the emergency drainage, the patient is alive with no evidence of recurrence. After drainage for rectal carcinoma complicated by Fournier's gangrene, the possibility of recurrence around the drainage site should be considered.

A 58-year-old woman presenting with abdominal distension was diagnosed with a tumor in the right ovary. A chest-abdominal-pelvic computed tomography scan revealed multiple lung metastases, multiple liver metastases, and peritoneal dissemination. Invasion of the rectum by peritoneal dissemination of the Douglas' pouch was suspected. She was diagnosed with Stage Ⅳ right ovarian cancer and was treated with preoperative chemotherapy. After chemotherapy, debulking surgery of the abdominal cavity (total hysterectomy, bilateral salpingo-oophorectomy, partial omentectomy, and Hartmann's procedure) was performed. Because there was swelling observed in multiple mesorectal lymph nodes, lymph node dissection was performed based on methods used for rectal cancer surgery. Postoperative histopathological examination revealed multiple mesorectal lymph node metastases arising from ovarian cancer. We suggest that mesorectal lymph node dissection be considered a part of debulking surgery for ovarian cancers that have invaded the rectum.

The patient was a 73-year-old woman. She underwent right hemicolectomy and D3 lymph node dissection for cecal cancer in June 2003. Although a peritoneal dissemination was intraoperatively noted around the primary tumor lesion, it was resected concurrently and thus R0 surgery was accomplished. Postoperative adjuvant chemotherapy was not performed. During the follow-up on an outpatient basis, a solitary left lung metastasis was found and partial left upper lobectomy of the lung was performed in December 2004. A solitary liver metastasis was identified in the liver (S3), and lateral segmentectomy of the liver was performed in June 2007. The patient was alive with no evidence of recurrence 11 years and 9 months after resection of the primary lesion and 7 years and 9 months after the hepatectomy. Long-term survival can be achieved by performing resection without residual cancer even in some cases with metachronous metastatic recurrences in multiple organs. Metastasectomy should be considered proactively when the patient is in a good general condition and R0 resection is possible.

SummaryBackground and aimsTransthoracic esophagectomy using 3-field lymphadenectomy (TTE-3FL) for esophageal cancer is one of the most aggressive gastrointestinal surgeries. Early enteral nutrition (EN) for TTE-3FL patients is useful and valid for early recovery; however, EN using a fat-containing formula risks inducing chyle leak. In the present study, we retrospectively examined esophageal cancer patients treated byTTE-3FL and administered postoperative EN to elucidate the validity of lowering the fat levels in elemental formulas to prevent postoperative chyle leak and improve postoperative recovery.MethodsA total of 74 patients who received TTE-3FL for esophageal cancer were retrospectively examined. Patients were classified into two groups according to the type of postoperative EN: Group LF patients received a low-fat elemental formula, and Group F patients received a standard fat-containing polymeric formula. The following clinical factors were compared between the groups: EN start day, maximum EN calories administered, duration of respirator use, length of ICU stay, incidence of postoperative infectious complications, use of parenteral nutrition (PN), and incidence of postoperative chyle leak.ResultsPatients in Group LF were started on EN significantly earlier after surgery and they consumed significantly higher maximum EN calories compared to Group F patients (P