Room-Temperature Phosphorescence and Cellular Phototoxicity Activated by Triplet Dynamics in Aggregates of Push-Pull Phenothiazine-Based Isomers.

In this study, we report a comprehensive time-resolved spectroscopic investigation of the excited-state deactivation mechanism in three push-pull isomers characterized by a phenothiazine electron donor, a benzothiazole electron acceptor, and a phenyl π-bridge where the connection is realized at the relative ortho, meta, and para positions. Spin-orbit charge-transfer-induced intersystem crossing takes place with high yield in these all-organic donor-acceptor compounds, leading also to efficient production of singlet oxygen. Our spectroscopic results give clear evidence of room-temperature phosphorescence not only in solid-state host-guest matrices but also in highly biocompatible aggregates of these isomers produced in water dispersions, as rarely reported in the literature. Moreover, aggregates of the isomers could be internalized by lung cancer and melanoma cells and display bright luminescence without any dark cytotoxic effect. On the other hand, the isomers showed significant cellular phototoxicity against the tumor cells due to light-induced reactive oxygen species generation. Our findings strongly suggest that nanoaggregates of the investigated isomers are promising candidates for imaging-guided photodynamic therapy.

Early results and complications of colorectal laparoscopic surgery and analysis of risk factors in 492 operated cases.

This study aimed to evaluate the early results of colorectal laparoscopic surgery with special attention to surgical and medical complications. The risk factors of such surgery are also investigated on the basis of a large series of operated cases: the preoperative knowledge of such factors could guide the operative program and the postoperative treatment with reduction of complications and improvement of the outcome. Between 1998 and 2008, 492 patients had been submitted to colorectal laparoscopic surgery by the same team: 387 for cancer and 105 for benign disease. All colorectal surgical operations are included in the series. No selection of the patients was made: laparoscopy was performed in all cases accepting the procedure. Several risk factors have been analysed in cases of fistula (age, pathology sex, type of the operation, cancer stages, preoperative radiochemotherapy, stool diversion and team experience) and in cases of medical complications (age, pathology, cancer stages and type of operation). The overall results in this series of laparoscopic colorectal operated cases are similar to other results published at present by the main surgical Department all over the world; no mortality and low number of medical (2.4%) and surgical complications (9.3%), with no differences also with the best open surgery series. Complete or partial conversion to open surgery was required in few cases (1.2%) and same others (1.4%) were operated again for bleeding or sudden anastomotic leakage. Regarding the risk factors in such surgery, a good correlation has been discovered between anastomotic leakage and the team experience, the age over 70 of the patients, the rectal tumour site in man, the advanced tumour stages, the previous radiochemotherapy, while medical complications seem to depend on advanced patients age and advanced cancer stages. Laparoscopic colorectal surgery at present is going to be considered the gold standard in the large majority of colorectal diseases including all cancer stages in the preoperative balance and in the early postoperative follow-up a special attention is required to same risk factors like the advanced patients age, the extended cancers, the low positioned rectal tumours. Complications are more frequent at the beginning of the experience of the surgical team and if more than one risk factors coexist, but it do not represent contraindication to laparoscopic surgery.

Solitary true cyst of the pancreas in adults. A report of two cases.

CONTEXT: Solitary true cysts of the pancreas in adults are extremely rare and only few cases have been reported in the literature. The etiology and natural history of these lesions remain unknown and treatment is not standardized. We describe two additional resected cases. CASE REPORTS: The first patient was a young woman with an incidental 3 cm cyst located in the pancreatic head who underwent enucleation. The second patient was a young woman with a large 8 cm symptomatic cyst located in the pancreatic tail who underwent a laparoscopic spleen-preserving distal pancreatectomy. Histological examination revealed fibrous walls lined by a monolayer of cuboidal epithelium in both cases. CONCLUSIONS: A preoperative work-up alone does not always allow an accurate diagnosis, but it is useful in determining lesion characteristics and guiding therapeutic decision making. When surgery is indicated, a limited resection is warranted in most cases.

Adenocarcinoma of the esophagogastric junction: the role of abdominal-transhiatal resection.

The surgical strategy for adenocarcinoma of the esophagogastric junction is still controversial. The aim of this study was to evaluate surgical results of the abdominal-transhiatal approach for 100 consecutively operated type II and III cardia adenocarcinoma, to clarify clinicopathological differences between these tumors, and to define prognostic factors. A prospectively maintained database identified 100 consecutively operated patients with Siewert type II and III cardia adenocarcinoma. Survival was analyzed by the Kaplan-Meier method. Differences between subgroups and prognostic factors were evaluated by the log rank test and Cox regression. Concerning clinicopathological characteristics, only the incidence of T1-2 stage was significantly higher in Siewert II type (P = .006). A complete (R0) resection was obtained in 74 patients (74%). Overall postoperative mortality and morbidity rates were 6% and 28%, respectively. Overall actuarial 5-year survival rate in resected patients was 27.4% (median 27 months), with 20.6% for type II and 34 for type III cancers (P = .07). Considering R0 resections, overall actuarial 5-year survival rate was 33.9% (median 33 months), with 26.7% for type II and 40.5 for type III cancer (P = .06). Pathologic T and N stage and R status were independent prognostic factors by multivariate analysis, and Siewert type showed a trend toward significance. The abdominal-transhiatal approach is a safe surgical approach, allowing complete tumor resection and adequate lymphadenectomy in these patients. True carcinoma of the cardia may be a distinct clinical entity with a more aggressive natural history than subcardial gastric carcinoma.

Genetic screening for LRRK2 gene G2019S mutation in Parkinson's disease patients from Southern Italy.

Leuchine-rich repeat kinase 2 (LRRK2) gene mutations are a common cause of familial and sporadic Parkinson disease (PD). G2019S is the most frequent mutation of the LRRK2 gene and has been reported in about 5-6% of familial and 1-2% of sporadic PD cases. The aim of this study is to investigate the G2019S frequency in a series of 58 familial and 70 sporadic PD patients recruited from Campania, a region in Southern Italy. We identified one heterozygous G2019S mutation in a PD patient who also suffered from obsessive disorder and depression and presented hallucinations and delusional jealousy while he was treated with l-dopa, pramipexole, and amantadine. Brain (18)F-deoxy-glucose PET showed relative decrease of glucose metabolism in the caudate nuclei and to a lesser extent in cortical parietal/frontal regions. The patient's mother also had PD and molecular analysis demonstrated that she carried the same mutation. G2019S mutation frequency is rather low in overall patients (0.8%) and in the familial group (1.7%), suggesting that it may be an uncommon cause of PD in Southern Italy.

Nigrostriatal involvement in ataxia with oculomotor apraxia type 1.

Ataxia with oculomotor apraxia type 1 (AOA1) is a rare autosomal recessive neurodegenerative disease, recently associated with mutations in the aprataxin gene. Main features are early onset cerebellar ataxia, oculomotor apraxia and peripheral neuropathy. The presence of choreoathetosis or dystonia in some patients suggests basal ganglia involvement, but these structures appear preserved in a single case in which neuropathological examination was performed. To evaluate in vivo the nigrostriatal function we studied dopamine transporter (DAT) density with [(123)I] 2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FPCIT)-SPECT in four AOA1 patients and eight healthy volunteers. All patients showed ataxia and neuropathy; only one had chorea and none had dystonia. Comparing with controls, AOA1 patients showed a slight reduction of the average striatal DAT density, which was bilateral and uniform in caudate and putamen. Nigrostriatal impairment occurred even in the absence of extrapyramidal features. Our data suggest subclinical involvement of basal ganglia in AOA1.

Isolated pancreatic metastasis of extremity myxoid liposarcoma: Report of a case.

Myxoid liposarcoma (ML) has a high predilection for extrapulmonary sites of metastases, including intra-abdominal metastases, but pancreatic involvement is extremely rare. Here, we report the case of a 66-year-old male patient, who underwent pancreaticoduodenectomy for isolated pancreatic metastasis of ML of the left lower extremity that had been excised 6 years before. Completion pancreatectomy was necessitated afterwards for a delayed haemorrage associated with pancreatic fistula. Currently the patient is alive with no evidence of disease. Highly selected patients with isolated pancreatic metastasis of soft tissue sarcoma may benefit from a curative surgical resection.

PINK1 homozygous W437X mutation in a patient with apparent dominant transmission of parkinsonism.

We analyzed the PINK1 gene in 58 patients with early-onset Parkinsonism and detected the homozygous mutation W437X in 1 patient. The clinical phenotype was characterized by early onset (22 years of age), good response to levodopa, early fluctuations and dyskinesias, and psychiatric symptoms. The mother, heterozygote for W437X mutation, was affected by Parkinson's disease and 3 further relatives were reported affected, according to an autosomal dominant transmission.

Novel mutation of SACS gene in a Spanish family with autosomal recessive spastic ataxia.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an inherited neurodegenerative disorder characterized by early-onset, spastic ataxia and peripheral neuropathy. It was originally described in an inbred population of Quebec and later in some other countries. We report a new missense SACS mutation (7848C>T) in a Spanish family whose phenotype is similar to that of the previously described ARSACS patients. 7848C>T is the first SACS mutation reported in Spain confirming worldwide distribution of the disease.

Laparoscopic surgery for gastric cancer: preliminary experience.

BACKGROUND: Laparoscopic surgery for gastric cancer (GC) was introduced in the past decade because it was considered less invasive than open surgery, resulting in less postoperative pain, faster recovery, and improved quality of life. Several studies have demonstrated the safety and feasibility of this procedure. We analyzed our preliminary experience with this procedure. METHODS: From November 2003 to December 2004, 20 patients affected by gastric adenocarcinoma were operated on with a totally laparoscopic or laparoscopic-assisted approach. This series included 10 women and 10 men, aged from 34 to 75 years. Procedures consisted of eight total gastrectomies, three subtotal Billroth I and seven Billroth II gastrectomies, one proximal gastrectomy, and one wedge resection. According to the TNM classification, we observed five patients at stage Ia, four at stage Ib, three at stage II, one at stage IIIa, two at stage IIIb, and five at stage IV. RESULTS: In all patients the procedures were completed without any conversion. Operative time ranged from 150 to 300 min. The number of dissected lymph nodes ranged from 23 to 47. No mortality was observed. Overall morbidity rate was 10% (two cases), with one enteric fistula and one esophagojejunal anastomotic leakage associated with pancreatitis. Excluding these two patients, postoperative stay was between 12 and 20 days. CONCLUSIONS: Even though accompanied by a difficult learning curve, safety and feasibility are widely demonstrated, but a skilled and experienced surgeon is required. Accurate selection of patients is mandatory and curative resection is achievable in cases where GC is not advanced.

Extended multiorgan resection for T4 gastric carcinoma: 25-year experience.

BACKGROUND AND OBJECTIVES: In locally advanced gastric carcinoma infiltrating adjacent organs, an extended resection including invaded organs is required to improve the prognosis. We retrospectively analyzed our experience with extended multiorgan resection (EMR) in patients with advanced gastric cancer. METHODS: Between December 1979 and April 2004, 65 patients were resected for extended gastric carcinoma macroscopically invading other organs. Various clinicopathologic factors influencing early and late results were evaluated. Survival rates were calculated according to the Kaplan-Meier method. Prognostic factors were evaluated by univariate and multivariate analysis. RESULTS: The majority of patients (61.5%) did receive a R0 curative resection. In 52 (80%) of the 65 presumed T4 cancers, histologic final analysis confirmed invasion. Postoperative morbidity and mortality was 27.7% and 12.3%, respectively. Actuarial 5-year overall survival (OS) rate was 21.8%. It was significantly better in R0 versus R+ (30.6% vs. 0%, P = 0.001). Multivariate analysis identified curative resection as the strongest predictor of survival (P = 0.002). CONCLUSIONS: Patients with locally advanced gastric carcinoma invading adjacent organs can benefit from aggressive surgical treatment with acceptable morbidity and mortality. However, curative resection is mandatory to improve prognosis.

The R495W mutation in SPG3A causes spastic paraplegia associated with axonal neuropathy.

Mutations in the SPG3A gene cause a form of pure, early-onset autosomal dominant hereditary spastic paraplegia linked to chromosome 14q. The encoded protein, atlastin, is a putative member of the dynamin superfamily of large GTPases involved in cellular trafficking patterns. We report a new atlastin mutation causing spastic paraplegia in association with axonal neuropathy in an Italian family.

Treatment for isolated loco-regional recurrence of gastric adenocarcinoma: does surgery play a role?

AIM: To evaluate the role of surgical treatment for isolated loco-regional recurrences of operated gastric adenocarcinoma. METHODS: Among the 837 patients operated for gastric adenocarcinoma between December 1979 and April 2004, 713 (85%) underwent resection with curative intent. A retrospective review of a prospectively collected gastric cancer database was carried out. Overall recurrence rate was 44% (315 cases), with 75% occurring within the first 2 years from the operation. Isolated L-R recurrences were observed in 38 (12%) patients. Symptomatic lesions were observed in 27 (71%). RESULTS: Six (16%) patients were macroscopically resected with curative intent. The recurrence was located in the gastric stump after a STG in three patients, in the esophagojejunal anastomosis after a TG in two patients and in the gastric bed after a TG in one patient. Surgical procedures consisted of three secondary TG, two esophagojejunal resection and one excision of an extraluminal recurrence. Postoperative complications occurred in two patients (33%), including one anastomotic leakage and one hemorrhage. The latter patient died of sepsis 35 d after the surgery (mortality rate 17%). All patients died of recurrent gastric cancer: 2 within 1 year from surgery (8 and 11 mo, respectively), 2 after 16 and 17 mo respectively and 1 after 28 mo from the second operation. CONCLUSION: Surgery plays a very limited role in the treatment for isolated loco-regional recurrence of gastric adenocarcinoma.

Malignant haemangiopericytoma of the mesorectum.

The authors report the case of a malignant haemangiopericytoma found in an uncommon location, namely the mesorectum. Haemangiopericytomas of the mesorectum are rare mesenchymal tumours of vascular origin that usually occur in the musculature of the extremities, retroperitoneum, pelvis (uterus, ovary and urinary bladder), head, neck and lungs. Rare sites include the liver, pancreas, stomach and greater omentum. Because of their rarity the overall experience has not been significant and little has been published concerning such tumours. In addition, the difficult interpretation of the histological evidence and the poor prognosis of the disease may still give rise to problems in terms of clinical management. Haemangiopericytomas of the retrorectal space, however, seem to behave like malignant tumours: the clinical course is poor and survival short, despite radical surgery, due to early distant metastases and local recurrence. Surgery still remains the mainstay of treatment. Adjuvant therapies should be considered.

The treatment of large midline incisional hernias using a retromuscular prosthetic mesh (Stoppa-Rives technique).

Incisional hernia is a common problem after abdominal surgery. Many repair techniques with prosthetic meshes have been proposed but there is no general agreement as to the best choice. Our retrospective experience with 35 patients treated using a large polypropylene mesh placed beneath the rectus muscles and above the peritoneum (Stoppa-Rives technique) is reported. There was no operative mortality. Major postoperative complications occurred in 7 (20%) patients. Wound infection developed in 5 (14.2%) patients and in one case the mesh had to be removed. The recurrence rate was 2.8%. In conclusion, retrorectus preperitoneal mesh repair is an effective technique with a low recurrence rate and very few postoperative complications.