HSF-1/miR-145-5p transcriptional axis enhances hyperthermic intraperitoneal chemotherapy efficacy on peritoneal ovarian carcinosis.

Hyperthermic intraperitoneal administration of chemotherapy (HIPEC) increases local drug concentrations and reduces systemic side effects associated with prolonged adjuvant intraperitoneal exposure in patients affected by either peritoneal malignancies or metastatic diseases originating from gastric, colon, kidney, and ovarian primary tumors. Mechanistically, the anticancer effects of HIPEC have been poorly explored. Herein we documented that HIPEC treatment promoted miR-145-5p expression paired with a significant downregulation of its oncogenic target genes c-MYC, EGFR, OCT4, and MUC1 in a pilot cohort of patients with ovarian peritoneal metastatic lesions. RNA sequencing analyses of ovarian peritoneal metastatic nodules from HIPEC treated patients unveils HSF-1 as a transcriptional regulator factor of miR-145-5p expression. Notably, either depletion of HSF-1 expression or chemical inhibition of its transcriptional activity impaired miR-145-5p tumor suppressor activity and the response to cisplatin in ovarian cancer cell lines incubated at 42 °C. In aggregate, our findings highlight a novel transcriptional network involving HSF-1, miR145-5p, MYC, EGFR, MUC1, and OCT4 whose proper activity contributes to HIPEC anticancer efficacy in the treatment of ovarian metastatic peritoneal lesions.

European single-center experience on 356 operated patients for gastric cancer.

AIM: Surgery in association with lymphadenectomy is the treatment of choice for the gastric adenocarcinoma. Aim is to report our experience in the surgical treatment of gastric cancer in a European center. MATERIAL AND METHODS: A prospectively maintained database identified 515 patients. Staging laparoscopy was performed to rule out peritoneal carcinomatosis in suspicious cases. Type of surgery and lymphadenectomy were determined according to the Japanese guidelines and pathological staging according to the TNM classification. Survival was analysed using the Kaplan-Meier method. RESULTS: Staging laparoscopy avoided 150 (29.1%) unnecessary laparotomies. A total of 356 patients underwent surgery with curative intent. Overall postoperative morbidity and mortality rates were 16.8% and 5.9%, respectively. Two hundred-fifty-one patients (70%) were T3-T4. Negative lymph-nodes were observed in 71 patients (19.9%). One-hundred- seventy-nine were at least stage III. At a mean follow-up of 80.6 months, the overall and disease-free survival rates were 54.4% and 50.6%, respectively. The survival stratification based on the type of lymphadenectomy showed an overall survival rate of 43% and 65.5% in case of D1 and D2 lymphadenectomy, respectively. Based on the tumor stage the overall survival rate was 90%, 62.7%, 36.4% and the disease-free survival was 90%, 54.3%, 31.3%, for stage I, II and III, respectively. CONCLUSIONS: Total or subtotal gastrectomy with D2 lymphadenectomy and adjuvant therapy for the treatment of locally advanced gastric cancer proved a valuable strategy. Staging laparoscopy is recommended. KEY WORDS: Gastric cancer, Laparoscopy, Lymphadenectomy, Prognosis, Surgery.

Transanal drainage tube: alternative option to defunctioning stoma in rectal cancer surgery?

BACKGROUND: Anastomotic leakage (AL) remains the most dreaded complication after rectal cancer surgery. The aim of this study was to evaluate the role of transanal drainage tube in reducing the incidence, severity and hospital costs respect to defunctioning stoma (DS). METHODS: Considering 429 patients consecutively operated for rectal adenocarcinoma, the tube was placed in 275 (Group A) and not placed in 154 (Group B) patients. A DS was created in a subgroup of 54 patients among the latter. RESULTS: The incidence of AL was significantly higher in Group B (P=0.007). In patients with DS, the incidence was higher than Group A (P=NS). Grade C complications were significantly higher in Group B (P=0.006) and Grade B complications were significantly higher in patients with DS (P=0.03). Estimated economic benefit was 4,000 Euros for each patient. CONCLUSIONS: Transanal drainage tube may be a safe and effective alternative to DS in many cases. The incidence of leakage and Grade C complications are reduced albeit not significantly but Grade B complications are significantly lower. Although the AL incidence was similar in our experience, the tube allows to avoid a stoma-related consequence and the need for reversal procedure with economic benefit.

An 18-Year Experience in Diagnostic Laparoscopy of Peritoneal Carcinomatosis: Results from 744 Patients.

BACKGROUND: Despite accurate preoperative imaging assessment, optimal cytoreductive surgery with hyperthermic intraperitoneal chemotherapy remains unfeasible in many patients with peritoneal carcinomatosis at the time of surgery. The aim of this study was to evaluate the role of diagnostic laparoscopy in the selection of candidates. METHODS: Prospectively collected data of all patients undergoing diagnostic laparoscopy in our Department were retrospectively analyzed. Demographics and perioperative features as well as operative details and outcome were evaluated. RESULTS: The study included 744 consecutive patients. Primary ovarian tumors were the most common indications, followed by gastric tumors and recurrent colorectal cancers. The procedure was successfully completed in 99.73% of cases. Approximately two thirds of them (68%) had undergone previous surgical procedures. The presence of ascites was recorded in 482 patients (64.78%). A total of 374 (50.3%) patients were excluded from surgical exploration. Among those who eventually underwent surgery, CC0 resection was obtained in 64.6% (239) of cases. Understaging of peritoneal carcinomatosis was observed in 11 patients (1.48%). Postoperative mortality was null and 5 (0.8%) complications were observed. Three (0.4%) port-site metastases were recorded at the beginning of the experience. CONCLUSION: Diagnostic laparosocopy is a safe and feasible tool able to improve the selection of patients eligible for cytoreduction with hyperthermic intraperitoneal chemotherapy, at the same time allowing avoiding a significant number of unnecessary laparotomies.

Observations and considerations on a case of Mondor's syndrome associated with gigantomastia.

AIM: The study of the Mondor's syndrome as a possible complication of gigantomastia. MATERIAL AND METHOD: A 49 year old woman, with gigantomastia, came to our observation for the presence of a large superficial vein of the left breast affected by thrombophlebitis, compatible with Mondor's syndrome. RESULTS: A "Thorek" breast reduction was performed; the patient was discharged on the second postoperative day and the follow up was smooth and fee from any complications. DISCUSSION: In the case we observed, gigantomastia had a clear role in the pathogenesis of the Mondor's disease; in fact, the excessive weight of the breasts caused stretching of the mammary dorsal vein evolving in phlebitis. In literature, among the causes related to Mondor's disease the pendulous breast is described, probably with the same dynamic we have seen in this patient, but has never reported, so obviously, the correlation between the two events. It's considered as good practice in the pre-operative evaluation, to make differential diagnosis with any cancer, that, in a certain percentage, is associated with Mondor's syndrome, and once established the causes of the pathology, it is imperative to eliminate them to prevent any relapses. CONCLUSION: Among the various causes recognized as predisposing to Mondor's syndrome, there has never been described gigantomastia so far. The observation and treatment of a patient in whom the gigantomastia certainly led to the onset of Mondor's disease, has led us to consider this as one of the possible complications of gigantomastia, providing an additional cue to the treatment of this condition even at an early stage.

[Ectopic breast tissue and a carcinoma in atypical positions]. / Ectopie mammarie e carcinomi in sede atipica.

AIM: The aim of the study was to considerate neoplams of ectopic breast tissue in particular concerning the diagnostic and surgical related problems, analysing our experience in this extremely rare pathology. MATERIALS AND METHODS: A group of five women affected by neoplasm of ectopic breast tissuehave been examinated, four of them in axillary breast tissue and the other one in parasternal area. They came to our clinical observation (UOC BCG 21, UOC BCG 27-Policlinico Umberto I,-Università "Sapienza" di Roma) between 2006 and 2008. All the patient underwent surgical intervention in our department. DISCUSSION: According to the literature we can assess that this is a rare pathology and so the diagnostic and surgical choices are different from case to case depending on the size, the localization , the local invasion. CONCLUSIONS: This rare pathology can occur in many different forms and areas. This fact makes impossible to create a guideline of diagnosis and treatment. This one must be acted in respect of radicality and when it is possible, of aesthetic criteria.