Concanavalin A-Rose Bengal bioconjugate for targeted Gram-negative antimicrobial photodynamic therapy.

Photodynamic therapy (PDT) is considered a very promising therapeutic modality for antimicrobial therapy. Although several studies have demonstrated that Gram-positive bacteria are very sensitive to PDT, Gram-negative bacteria are more resistant to photodynamic action. This difference is due to a different cell wall structure. Gram-negative bacteria have an outer cell membrane containing lipopolysaccharides (LPS) that hinder the binding of photosensitizer molecules, protecting the bacterial cells from chemical attacks. Combination of the lipopolysaccharides-binding activity of Concanavalin A (ConA) with the photodynamic properties of Rose Bengal (RB) holds the potential of an innovative protein platform for targeted photodynamic therapy against Gram-negative bacteria. A ConA-RB bioconjugate was synthesized and characterized. Approximately 2.4 RB molecules were conjugated per ConA monomer. The conjugation of RB to ConA determines a decrease of the singlet oxygen generation and an increase of superoxide and peroxide production. The photokilling efficacy of the ConA-RB bioconjugate was demonstrated in a planktonic culture of E. coli. Irradiation with white light from a LED lamp produced a dose-dependent photokilling of bacteria. ConA-RB conjugates exhibited a consistent improvement over RB (up to 117-fold). The improved uptake of the photosensitizer explains the enhanced PDT effect accompanying increased membrane damages induced by the ConA-RB conjugate. The approach can be readily generalized (i) using different photo/sonosensitizers, (ii) to target other pathogens characterized by cell membranes containing lipopolysaccharides (LPS).

Phenotypic spectrum of STRA6 mutations: from Matthew-Wood syndrome to non-lethal anophthalmia.

Matthew-Wood, Spear, PDAC or MCOPS9 syndrome are alternative names used to refer to combinations of microphthalmia/anophthalmia, malformative cardiac defects, pulmonary dysgenesis, and diaphragmatic hernia. Recently, mutations in STRA6, encoding a membrane receptor for vitamin A-bearing plasma retinol binding protein, have been identified in such patients. We performed STRA6 molecular analysis in three fetuses and one child diagnosed with Matthew-Wood syndrome and in three siblings where two adult living brothers are affected with combinations of clinical anophthalmia, tetralogy of Fallot, and mental retardation. Among these patients, six novel mutations were identified, bringing the current total of known STRA6 mutations to seventeen. We extensively reviewed clinical data pertaining to all twenty-one reported patients with STRA6 mutations (the seven of this report and fourteen described elsewhere) and discuss additional features that may be part of the syndrome. The clinical spectrum associated with STRA6 deficiency is even more variable than initially described.

Immunohistochemical expression and prognostic significance of fatty acid synthase in pancreatic carcinoma.

BACKGROUND: The aim of this study was to evaluate immunohistochemical markers in pancreatic cancer and to determine the association of their expression with clinicopathological features and prognosis. PATIENTS AND METHODS: Thirty pancreatic adenocarcinoma patients were followed-up for an average period of 5 years. FAS, bcl-2, p53 and Ki-67 expression were detected immunohistochemically to determine their prognostic value. RESULTS: FAS was statistically associated with p53 (p = 0.002), Ki-67 (p = 0.003), higher histological grade (p = 0.001 and recurrence and overall survival (p = 0.001). CONCLUSION: The newly found overexpression of FAS in highly aggressive pancreatic carcinomas may help us stratify patients into different prognostic groups and indicate new therapeutic strategies.

Serum markers measured in FNA fluids of medullary thyroid carcinoma occurring as a cyst.

BACKGROUND: Diagnosis of medullary thyroid carcinoma (MTC) is still a challenge, and the measurement of calcitonin in fine-needle aspiration (FNA) washout has been recently introduced. Rarely, MTC presents as a cyst and its preoperative detection is difficult. METHODS: A 66-year-old woman was referred to us with high serum calcitonin. Ultrasound evaluation showed one cystic and one solid nodule. FNA was performed in both nodules and calcitonin, procalcitonin and CEA were measured in the aspirate fluids. RESULTS: The markers showed elevated levels in the FNA washout of the cyst and the patient was operated on. Final histology demonstrated MTC of the cystic nodule. Four weeks later, all serum markers were undetectable. CONCLUSIONS: In the presence of a cystic thyroid lesion the diagnosis of MTC should be taken into account, and measuring calcitonin in FNA fluid is relevant. The determination in FNA of other markers is technically feasible but its role should be evaluated in larger series.

Videolaparoscopic total and subtotal gastrectomy with extended lymph node dissection for gastric cancer.

BACKGROUND: Laparoscopic surgery has been used in the treatment of early gastric cancer with low mortality and morbidity and improvement in patient's quality of life. The purpose of the current study was to determine if these advantages persist after radical laparoscopic treatment of more advanced gastric cancer. METHODS: A retrospective review of 44 patients after laparoscopic surgery for gastric cancer was performed. RESULTS: Tumor stage was IA in 8 patients, IB in 12, II in 9, IIIA in 6, IIIB in 1, and IV in 8. Eight total and 36 subtotal R0 gastrectomies were performed (12 D(1) and 32 D(2)). The mean number of dissected lymph nodes was 38.1 +/- 21.5. Conversion rate was 7%. Operative mortality and morbidity were 7% and 12%, respectively. Three-year survival was 75%. CONCLUSIONS: Laparoscopic radical total or subtotal gastrectomy with extended lymphadenectomy for gastric cancer is a feasible, safe, and oncologically effective procedure.

[Sentinel lymph node in breast cancer: experience of 4 years]. / Il linfonodo sentinella nel cancro della mammella: 4 anni di esperienza.

The aim of the study was to describe our experience with sentinel lymph node biopsy in patients with breast cancer. 326 consecutive patients with breast cancer operated on from December 1998 to December 2002 were studied. All patients gave their informed consent. Patients were mapped with an intradermal injection of Tc-99 (median dose: 0.5 mCi) and/or Patent Blue. Sentinel lymph nodes were analyzed with serial sections. 333 procedures were performed in the 326 patients. A median of two sentinel lymph nodes were identified in 322 cases (97%). 3165 additional non-sentinel lymph nodes were removed and analyzed to assess the accuracy of the technique. The correlation between sentinel lymph nodes and final pathological status was 97% (314/322). In 66/133 cases with axillary metastases (50%) the sentinel lymph node was the only site of metastasis. Micrometastases were diagnosed in 35/66 cases (26%), while isolated tumour cells were found in 15 cases (11%). At a median follow-up of 21 months one patient presented an axillary relapse (0.3%). Our experience confirms that sentinel lymph node biopsy is accurate and reproducible. Routine axillary dissection is no longer the gold standard in patients with early breast cancer. Prospective studies are under way in an attempt to provide, definitive answers.

Human papillomavirus type 16 DNA detected in pulmonary metastases from a penile squamous cell carcinoma: a case study.

This report describe the case of a patient presenting with pulmonary metastases from a penile cancer, where the presence of the human papillomavirus (HPV) type 16 DNA both in the primary tumor and in the distant metastases confirmed the spreading of the disease, ruling out a possible primary lung squamous cell carcinoma. Indeed, according to the findings, the HPV genotyping test might help in the identification of metastatic disease from anogenital malignancies or other HPV-related cancers.

Intraoperative examination of sentinel nodes in breast cancer: is the glass half full or half empty?

BACKGROUND: Intraoperative identification of positive sentinel lymph nodes in patients with breast cancer may avoid a return to the operating room. METHODS: In a group of 402 consecutive patients with primary breast cancer who underwent sentinel lymph node biopsy, an intraoperative examination (IE) was obtained in 236 cases either by frozen section (FS; n = 68) or by touch preparation cytology (TP; n = 168). RESULTS: IE had an accuracy of 89% (209 of 236), but it identified only 52 of 77 positive cases (sensitivity, 68%). There were 25 false-negative cases (13.7%), of which 7 were macrometastases and 18 by micrometastases (P < .001). Six macrometastases were missed by TP and one by FS (P = .9). There were two false-positive cases (3.7%). Overall, 48 (20%) of 236 patients avoided a delayed return to the operating room for a completion lymphadenectomy because of IE findings. This occurred in 10% of patients with tumors <1 cm in diameter, in 20% of those with tumors between 1 and 2 cm, and in 34% of those with tumors >2 cm in diameter (P = .05). The cost savings for the Italian Health System amounted to 198,040 (US$223,794) in these patients. CONCLUSIONS: IE has acceptable sensitivity for lymph node macrometastases, but it is a weak tool for diagnosing micrometastases. FS and TP are roughly equivalent. IE allows management changes, because approximately 20% of all patients are expected to undergo synchronous axillary dissection, and it is particularly helpful in T2 patients. This may allow substantial cost savings for the health-care system.