Therapeutic options for body packers: surgical or conservative treatment? A single center experience and review of literature.

UNLABELLED: Body packing is a way to deliver packages of drugs hidden in body cavities. In Europe, as noted the latest report coming from the Brussels observatory, there are 74 million drugs consumers. Italy is in pole position and Perugia was considered as a "capital city" in the drug market. Body packers usually swallow the drug packets, although their insertion into the rectum and vagina has also been reported. The management depends on whether or not the patient becomes symptomatic. Surgery is indicated in presence of repeated bouts of drug toxicity not controlled by medical treatment, radiological evidence of packet retention in the stomach, intestinal obstruction or perforation. It is also important to emphasize that, in a multidisciplinary context, the patient's management before reaching the operating theater if symptomatic, is aimed to stabilization and is usually demanded to Intensive Care Unit (ICU) physicians. We present our center recent experience with body packers, managed both with surgical and conservative treatments. KEY WORDS: Body packers, Drugs, Emergency surgery, Foreign bodies.

DNA damage response markers are differentially expressed in BRCA-mutated breast cancers.

Cells have stringent DNA repair pathways that are specific for each different set of DNA lesions which is accomplished through the integration of complex array of proteins. However, BRCA-mutated breast cancer (BC) has defective DNA repair mechanisms. This study aims to investigate differential expression of a large panel of DNA repair markers to characterise DNA repair mechanisms in BRCA-associated tumours compared to sporadic tumours in an attempt to characterise these tumours in routine practice. Immunohistochemistry and tissue microarray technology were applied to a cohort of clinically annotated series of sporadic (n = 1849), BRCA1-mutated (n = 48), and BRCA2-mutated (n = 27) BC. The following DNA damage response (DDR) markers are used; BRCA1, BRCA2, RAD51, Ku70/Ku80, BARD, PARP1 (cleaved), PARP1 (non-cleaved), and P53 in addition to basal cytokeratins, ER, PR, and HER2. A significant proportion of BRCA1 tumours were positive for PARP1 (non-cleaved), and negative for BARD1 and RAD51 compared with sporadic BC. BRCA2 tumours were significantly positive for PARP1 (non-cleaved) compared with sporadic tumours. RAD51 was significantly higher in BRCA1 compared with BRCA2 tumours (p = 0.005). When BRCA1/2 BCs were compared to triple-negative (TN) sporadic tumours of the studied DDR proteins, BARD1 (p < 0.001), PARP1 (non-cleaved) (p < 0.001), and P53 (p = 0.002) remained significantly different in BRCA1/2 tumours compared with TN BC. DNA repair markers showed differential expression in BRCA-mutated tumours, with a substantial degree of disruption of DNA repair pathways in sporadic BC especially TN BC. DNA double-strand break (DSB) repair is assisted by PARP1 expression in BRCA-mutated tumours, whereas the loss of DSB repair via RAD51 is predominant in BRCA1 rather than BRCA2 BC.

Biological and clinical significance of PARP1 protein expression in breast cancer.

Poly(ADP-ribose) polymerase-1 (PARP1) is a key facilitator of DNA repair. PARP inhibitors have gained recent attention as promising therapeutic agents for the treatment of solid tumours including breast cancer (BC). However, the biological and clinical significance of PARP1 expression in BC and its role in DNA-damage response (DDR) remain to be defined. We investigated the expression of PARP1 expression, cleaved (PARP1c) and non-cleaved (PAR1nc) forms, in a large and well-characterised cohort of clinically annotated stage I-III operable BCs (n = 1,269) and 43 BRCA1-mutated BCs using immunohistochemistry. PARP1 expression was correlated to clinicopathological variables, outcome and expression of other key DNA repair proteins (BRCA1, RAD51, Ku70/80, PIASγ and CHK1). Expression of PARP1 was exclusively nuclear. 49 and 85 % of sporadic BC showed expression PARP1nc and PARP1c, respectively. In BRCA1-mutated tumours, PARP1nc/PARP1c was highly expressed (95 and 79 %, respectively). PARP1nc expression was positively associated with premenopausal younger age patients, larger size and higher tumour grade. PARP1 was positively associated with DDR-proteins; RAD51, BRCA1, CHK1 and PIASγ (p < 0.001). Negative association was found between PARP1nc and Ki67. PARP1c was associated with ER (p < 0.001). Different associations between PARP1 and DDR-proteins were observed when stratified based on ER/BRCA1 status. PARP1 was not an independent predictor of outcome in sporadic or BRCA1-mutated BC. Our results demonstrate a potential biological role for PARP1c and PARP1nc in DNA repair in BC based on the significant association with other key DNA damage repair proteins. These associations were not restricted to ER-negative or triple-negative subgroup.

Incidental finding of carcinoid tumor on Meckel's diverticulum: case report and literature review, should prophylactic resection be recommended?

Meckel's diverticulum (MD) is the most common congenital anomaly of the gastrointestinal tract and is caused by incomplete obliteration of the vitelline duct during intrauterine life. MD affects less than 2% of the population. In most cases, MD is asymptomatic and the estimated average complication risk of MD carriers, which is inversely proportional to age, ranges between 2% and 4%. The most common MD-related complications are gastrointestinal bleeding, intestinal obstruction and acute phlogosis. Excision is mandatory in the case of symptomatic diverticula regardless of age, while surgical treatment for asymptomatic diverticula remains controversial. According to the majority of studies, the incidental finding of MD in children is an indication for surgical resection, while the management of adults is not yet unanimous. In this case report, we describe the prophylactic resection of an incidentally detected MD, which led to the removal of an occult mucosal carcinoid tumor. In literature, the association of MD and carcinoid tumor is reported as a rare finding. Even though the strategy for adult patients of an incidental finding of MD during surgery performed for other reasons divides the experts, we recommend prophylactic excision in order to avoid any further risk.

The integrated role of ultrasonography in the diagnosis of soft tissue metastases from melanoma: preliminary report of a single-center experience and literature review.

Currently melanoma has the fastest growing incidence of all cancers in men and the second in women (after lung cancer) in Western countries. Since prognosis of skin melanoma is excellent in early stages but dramatically worsens in advanced stages, an early diagnosis is fundamental in granting patients a favorable outcome. Sentinel node (SN) biopsy represents the gold standard for accurately staging melanoma, but other tests are commonly endorsed both in the initial staging work-up and in the follow-up, such as ultrasonography, computed tomography (CT)-scan and positron emission tomography (PET)-CT. PET-CT, among others, has high sensitivity and specificity for the study of distant metastases, the assessment of soft tissues and lymph node involvement, and for the guidance of surgical biopsies. Ultrasonography (US) is a non-invasive procedure whose use has recently expanded in our service, both preoperatively, intraoperatively and postoperatively, thanks to its wide availability, low costs and easy and fast reproducibility; ultrasonography even surpassed the reliability of PET-CT or CT-scan in the seven cases presented herein. US is operator-dependent, and this is probably the major limitation of the procedure, together with lack of prospective studies validating its strength, but our preliminary study demonstrates that ultrasound can assume an important role in melanoma, both for staging and the follow-up of patients, especially with lymph nodal or subcutaneous involvement.

Optimizing therapeutic timing in patients undergoing mastectomy through use of the Tiloop® synthetic mesh: single-step surgery.

Patients undergoing mastectomy for breast cancer have to face a long and elaborated therapeutic path, very often burdened by reoperation to replace the temporary expander, used to enlarge the submuscular pouch, with a definitive implant. Postoperative planning represents a critical moment of care, as it requires the integration of multiple treatments (chemotherapy, radiotherapy, hormonotherapy) each with a specific deadline. We believe that in such a complex multidisciplinary approach, coordination among the different therapeutic phases should be the key to success. The aim of the Breast Unit is to manage rapidly the ad hoc paths set out for each patient in order to guarantee compliance with adequate therapeutic timing. With this purpose in mind we tested the advantage of immediate reconstruction with definitive implants, by using a polypropylene mesh which, prolonging the inferolateral profile of the pectoralis major muscle (PMM), allows for direct accommodation of the desired implant volume. This leads to a single-step surgical approach, guaranteeing at the same time reduced interference with adjuvant therapies and good aesthetic results. We applied this technique to 4 patients, one of which was bilateral and, in spite of the restricted number of cases, our results seem to be promising.

Oncologic reliability of nipple-sparing mastectomy for selected patients with breast cancer.

BACKGROUND: Nipple sparing mastectomy (NSM) is the current surgical alternative to conventional techniques, when mastectomy is required. This less invasive procedure safeguards the integrity of the nipple areola complex (NAC), whose removal is recognized as a factor that exacerbates the patient's feeling of mutilation, however ensuring oncological radicality for women with breast cancer. PATIENTS AND METHODS: From January 2003 to January 2011, 77 patients underwent Nipple Sparing Mastectomy (NSM). Patients were carefully selected according to specific criteria. When requested, postoperative radiotherapy on the residual glandular tissue was performed within 6 months of surgery. Patients were on close clinical and instrumental follow-up every 4 months for 2 years and every 6 months for the remaining 3 years. RESULTS: Of the 77 patients who underwent NSM, 10 suffering from bilateral cancer were subjected to bilateral procedure, for a total of 87 performed procedures. Furthermore, in the same group, 13 NSMs were carried out for preventive purposes. The average diameter of resected tumors was 13.5 mm, with a range of 2 to 25 mm. During the follow-up (range 23-115 months, mean 50.33 months) 2 locoregional recurrences in the NAC were observed, identified through instrumental check, and surgically treated by NAC removal after 33 and 37 months respectively. CONCLUSION: According to the litterature data and confirmed by our experience, we consider NSM as an oncologically safe technique that, in the respect of inclusion criteria may be performed in any patient with indication to mastectomy. A careful selection of patients by a multidisciplinary team according to strict criteria is the key in determining feasibility as well as oncological safety and should lead the general acceptance and widespread use of such surgical technique.

Spontaneous splenic rupture in patient with metastatic melanoma treated with vemurafenib.

BACKGROUND: BRAF inhibitors such as vemurafenib are a new family of biological drugs, recently available to treat metastatic malignant melanoma. METHODS: We present the case of a 38-year-old man affected by metastatic melanoma who had been under treatment with vemurafenib for a few days. The patient suffered from sudden onset of abdominal pain due to intra-abdominal hemorrhage with profuse hemoperitoneum. An emergency abdominal sonography confirmed the clinical suspicion of a splenic rupture. RESULTS: The intraoperative finding was hemoperitoneum due to splenic two-step rupture and splenectomy was therefore performed. Histopathology confirmed splenic hematoma and capsule laceration, in the absence of metastasis. CONCLUSIONS: This report describes the occurrence of a previously unreported adverse event in a patient with stage IV melanoma receiving vemurafenib.

Appendiceal mucocele. A case report and literature review.

Appendiceal mucocele is a rare disease (0.3% of all appendectomy) and is characterized by the accumulation of mucoid material in the appendiceal lumen. Etiopathogenesis can be inflammatory or neoplastic. Four entities can be distinguished on the basis of histopathologic epithelial characteristics: simple appendiceal mucocele (AM), mucocele with epithelial hyperplasia, cystadenoma and cystadenocarcinoma; the last two subgroups represent neoplastic forms. Dissemination of neoplastic cells and mucoid material in abdominal cavity, caused by appendiceal perforation, clinically results in pseudomyxoma peritonei which is the dramatic evolution in 10-15% of cases. Clinically it can remain either asymptomatic for long time or it can manifest with abdominal pain that can be associated with the presence of a palpable mass. The most common clinical manifestation is pain in the right iliac fossa. Preoperative diagnosis is rare, while it is more frequently intraoperative. Therapy is fundamentally surgical: appendectomy is curative for simple AM, for AM with epithelial hyperplasia and for cystadenoma with intact appendiceal base; cecum resection is indicated for cystadenoma with larger base of implantation; right hemicolectomy has been the elective treatment in case of cystadenocarcinoma for several years although Gonzalez-Moreno and Sugarbaker have recently demonstrated its validity as definitive treatment only if it is performed in order to obtain complete cytoreduction, if there is lymph node involvement, or if histopathological examination indicates non-mucinous type. We report the case of a 60-year-old woman that presented with cystic neoformation in the right iliac fossa, that was preoperatively considered deriving from the ovary. We intraoperatively found the presence of appendiceal mucocele that histological examination defined as mucinous cystadenoma.

Ghost ileostomy after anterior resection for rectal cancer: a preliminary experience.

PURPOSE: The aim of this study was to describe and evaluate the feasibility and the eventual advantages of ghost ileostomy (GI) versus covering stoma (CS) in terms of complications, hospital stay and quality of life of patients and their caregivers after anterior resection for rectal cancer. METHODS: In this prospective study, we included patients who had rectal cancer treated with laparotomic anterior resection and confectioning a stoma (GI or CS), in the period comprised between January 2008 and January 2009. Short-term and long-term surgery-related mortality and morbidity after primary surgery (including that stoma-related and colorectal anastomosis-related) and consequent to the intervention of intestinal recanalization (CS group) and GI closure were evaluated. We evaluated hospital stay and quality of life of patients and their caregivers. RESULTS: Stoma-related morbidity rate was higher in the CS group than in GI group (37% vs. 5.5%, respectively, P = 0.04). Morbidity rate after intestinal recanalization in the CS group was 25.9% and 0% after GI closure (P = 0.08). Overall stoma morbidity rate was significantly lower in the GI group with respect to CS group (5.5% vs. 40.7%, respectively, P = 0.03). CS group was characterized by a significantly longer recovery time (P = 0.0002). Caregivers and stoma-related quality of life were better in the GI group than in CS group (P < 0.0001 and P = 0.0005, respectively). CONCLUSIONS: GI is feasible, characterized by shorter recovery, lesser degree of total, as well as anastomosis-related morbidity and higher quality of life of patients and the caregivers in respect to CS. We suggest that GI (should be evaluated as an alternative to conventional ileostomy) could be indicated in selected patients that do not present risk factors, but require caution for anastomotic leakage for the low level of colorectal anastomosis.