ST6Gal-I expression in ovarian cancer cells promotes an invasive phenotype by altering integrin glycosylation and function

Background

Ovarian adenocarcinoma is not generally discovered in patients until there has been widespread intraperitoneal dissemination, which is why ovarian cancer is the deadliest gynecologic malignancy. Though incompletely understood, the mechanism of peritoneal metastasis relies on primary tumor cells being able to detach themselves from the tumor, escape normal apoptotic pathways while free floating, and adhere to, and eventually invade through, the peritoneal surface. Our laboratory has previously shown that the Golgi glycosyltransferase, ST6Gal-I, mediates the hypersialylation of β₁ integrins in colon adenocarcinoma, which leads to a more metastatic tumor cell phenotype. Interestingly, ST6Gal-I mRNA is known to be upregulated in metastatic ovarian cancer, therefore the goal of the present study was to determine whether ST6Gal-I confers a similarly aggressive phenotype to ovarian tumor cells.

Methods

Three ovarian carcinoma cell lines were screened for ST6Gal-I expression, and two of these, PA-1 and SKOV3, were found to produce ST6Gal-I protein. The third cell line, OV4, lacked endogenous ST6Gal-I. In order to understand the effects of ST6Gal-I on cell behavior, OV4 cells were stably-transduced with ST6Gal-I using a lentiviral vector, and integrin-mediated responses were compared in parental and ST6Gal-I-expressing cells.

Results

Forced expression of ST6Gal-I in OV4 cells, resulting in sialylation of β1 integrins, induced greater cell adhesion to, and migration toward, collagen I. Similarly, ST6Gal-I expressing cells were more invasive through Matrigel.

Conclusion

ST6Gal-I mediated sialylation of β1 integrins in ovarian cancer cells may contribute to peritoneal metastasis by altering tumor cell adhesion and migration through extracellular matrix.     

Gastrointestinal stromal tumours: a broad spectrum of clinical presentations

Gastrointestinal stromal tumours, though rare, are the most common mesenchymal neoplasms affecting the gastrointestinal tract. The most frequent sites of origin are the stomach and the small bowel, but they can occur anywhere in the gastrointestinal tract. Mesenteric and retroperitoneal forms have been described. The Authors present their personal experience with the treatment of gastrointestinal stromal tumours, with particular reference to the broad spectrum of clinical presentations and to the consequent therapeutic implications. We report on a retrospective analysis of the clinical presentations and courses, surgical management and pathological features of 27 patients with such tumours treated in our institution from 1993 to 2005. The variables analysed were the morphological and clinical characteristics of the tumours, demographic data, type of surgical treatment and postoperative course. Long-term survival was evaluated on the basis of clinical and/or telephonic follow-up in all patients. One tumour was located in the oesophagus, 14 in the gastric area, 7 in the small bowel, 2 in the colon-rectum, and 3 in the peritoneum. All patients studied received radical surgical treatment. In 7 patients surgical resection was extended to other organs. No postoperative mortality or major postoperative complications were observed. Twenty-two patients are still alive at follow-up. Three patients died as a result of neoplastic relapse and 2 of other causes. The median survival was 36 months. The actuarial 3- and 5-year survival rates were 89.7% and 67.8%, respectively. Our experience indicates that the site of origin of gastrointestinal stromal tumours with their broad spectrum of clinical presentations may influence both the therapeutic choice (neoadjuvant utilisation of imatinib mesylate) and the surgical treatment (wedge resection vs enlarged operations).     

The use of anterior Caspar plate fixation in acute cervical spine injury

Optimal management of cervical cord injury in the presence of documented instability and/or compression of neural elements remains a controversial topic. Surgery and internal stabilization of cervical spine fracture/dislocations are effective and well accepted, but controversy exists on the relative merits of the anterior versus the posterior approach as well as the optimal timing of surgical intervention. We report our experience with the Caspar technique and instrumentation for anterior stabilization in 54 patients for acute cervical spine injury. Our series consists of 38 male and 16 female patients whose ages ranged from 16 to 68 years, with a mean age of 29.2 years. Thirty-two of these patients had complete neurological sensory/motor deficits at the time of presentation, eight were neurologically intact, and 14 had preservation of some motor and sensory function. All 54 patients had radiographic evidence of posterior instability as well as anterior disruption of either a vertebral body or intervertebral disk. We found that "early" intervention (less than 24 hours after injury) was performed frequently in the neurologically compromised patients. Twelve of the 22 patients undergoing surgery less than 24 hours after admission regained significant neurological function, with 13 of 22 developing postoperative complications. In the "delayed" group (surgery more than 24 hours after injury, mean 14.3 days), 14 patients experienced postoperative complications, with 15 of 24 demonstrating neurological improvement. The eight patients who were intact did uniformly well. There was no mortality during the follow-up. All 54 patients showed a solid fusion (clinically and radiologically) within 6 months of surgery. In two cases the plates had to be removed, without risking the fusion. Our experience suggests that although anterior cervical fusion and Caspar plating remain appropriate for patients with documented anterior compromise of the canal, it should not substitute for more traditional posterior stabilization procedures. Because this route has the potential for more serious complications, it should be reserved for the cases in which anterior decompression is deemed necessary or posterior fusion was unsuccessful. With appropriate selection of patients, no adverse effect of early surgery was demonstrated. In fact, neurologically compromised patients had the benefits of increased ease of patient care and early transfer to rehabilitation.     

Axillary Lymph Node Echo-Guided Fine-Needle Aspiration Cytology Enables Breast Cancer Patients to Avoid a Sentinel Lymph Node Biopsy. Preliminary Experience and a Review of the Literature

Purpose For many years, the status of the axillary lymph nodes has been determined by an axillary lymphadenectomy. However, a sentinel lymph node biopsy has been shown to effectively replace the need for an axillary lymphadenectomy in order to determine the axillary staging. This study presents the preliminary results regarding the efficacy of fine-needle aspiration cytology (FNAC) to identify metastatic axillary lymph nodes in the pre-operative phase. Methods One hundred lymph nodes from 100 patients with histologically and cytologically confirmed breast cancer (cT1–2 cN0) underwent echo-guided FNAC. The diagnostic accuracy (sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV]) for the axillary metastases was evaluated based on the histological findings of either a sentinel lymph node biopsy or an axillary lymphadenectomy as a reference standard. Results It was possible to avoid a sentinel lymph node biopsy in 30% of the cases; the sensitivity was 68%, specificity 100%, PPV 100%, and NPV 65%. Echo-guided FNAC of the axillary lymph nodes should thus be included among the regular diagnostic procedures of presurgical staging. Conclusion This simple, inexpensive, and minimally invasive technique makes it possible to avoid the additional cost of a sentinel lymph node biopsy while also sparing the patient the stress of undergoing a second surgery.     

Pancreatoduodenectomy for Tumors of Vater’s Ampulla: Report on 94 Consecutive Patients

Evaluation of prognostic factors of adenocarcinoma of Vater’s ampulla is still a matter of debate. The aim of this study was to evaluate retrospectively factors that influence early and long-term outcomes in a 20-year single-institution experience on ampullary carcinoma. A total of 94 consecutive patients with ampullary carcinoma or adenoma with severe dysplasia were managed from 1981 to 2002. Among them, 64 underwent pancreatoduodenectomy, and the remaining 30 submitted to surgical (n = 5) or endoscopic (n = 25) palliative treatment. Demographic, clinical, and pathologic data were collected, and a comparison was made between patients who did or did not undergo resection. Standard statistical analyses were carried out in an attempt to establish a correlation between clinical variables, intraoperative and pathologic factors, and survival in patients with resection. A total of 85 (90.4%) patients had potentially resectable lesions due to the extent of the tumor, but only 64 (68%) underwent curative resection. The surgical morbidity rate was 34.3%. Postoperative mortality was 9.3%, with no deaths among the 38 more recently treated patients. Median survivals were 9 and 54 months for nonresected and resected patients, respectively. The overall 5-year survival was 64.4% for patients undergoing pancreatoduodenectomy. Survival was found to be significantly affected by resection, tumor size, tumor grade, and tumor infiltration. Patients with negative lymph nodes show a trend toward longer survival. In a multivariate analysis, only the depth of tumor infiltration influenced patient survival.Pancreatoduodenectomy is the treatment of choice for ampullary carcinoma and adenomas with high-grade dysplasia, with a good chance of long-term survival. Surgical resection remains the most important factor influencing outcome.     

The modern treatment of early gastric cancer: our experience in an Italian cohort

Background  Endoscopic submucosal dissection (ESD) has been developed as treatment for early gastric cancer (EGC) by Japanese authors. However, there are no reports about its possible implementation in the Western setting. The aim of the present work is to determine the safety and efficacy of the endoscopic treatments for EGC in an Italian cohort. Methods  Forty-five patients for a total of 48 gastric lesions were enrolled in the study. Thirty-six EMR procedures were performed with the strip biopsy technique using a double-channel endoscope. En bloc resection refers to resection in one piece, while piecemeal refers to resections in which the lesion was removed in multiple fragments. A total of 12 ESD were performed and completed with IT knife. We define as curative treatment lateral and vertical margins of the resected specimens free of cancer and repeat endoscopic finding of no recurrent disease. Results  Out of 36 EMR procedures, 10 were piecemeal resections (28%), while 26 were en bloc (72%). ESD led to en bloc resection in 11/12 cases (92%). Histological assessment of curability in the EMR group was achieved in 56% of the cases, and in 92% of the ESD group. Mean follow-up period was 31 months (range: 12–71 months). There was no local recurrence or distant metastasis in the curative group patients. Conclusions  These results seem to confirm the safety and the clinical efficacy of the ESD procedure in the Western world too.     

Surgery: Independent Prognostic Factor in Curable and Far Advanced Gastric Cancer

The hospital records of 639 patients affected by primary gastric cancer who were consecutively admitted to our unit during the period 1981–1995 were reviewed. Overall 220 underwent total gastrectomy (38 palliative), 12 had resection of the gastric stump, 195 had distal subtotal gastrectomy (55 palliative), 78 had bypass procedures, 72 had explorative laparotomy, and 62 had no operation. Univariate and multivariate analyses were used to evaluate 5-year survival with respect to the main clinical, pathologic, and treatment variables after both curative and palliative treatments. Overall the 5-year survival after curative treatment (320 patients—operative mortality excluded) was 55.5%: 91.1% for stage IA, 71.5% IB, 62.4% II, 37.5% IIIA, 31.5% IIIB. Among patients who underwent palliative treatment 5-year survival was 13.1% after gastric resection (total or distal subtotal), 4.9% after the bypass procedures, 0 after explorative laparotomy, and 0 after no operation. Univariate and multivariate survival analyses showed that variables independently associated with poor survival were advanced stage, upper location and D1 lymphadenectomy after curative treatment, tumor spread to distant sites, and nonresectional surgery after palliative treatment. Multivariate analysis showed that even though survival with gastric cancer depends on predetermined factors, the type of surgery can have a significant effect on prognosis after both curative and palliative treatment.