[PANCREATIC NEUROENDOCRINE TUMORS (PNET): THE DILEMMA OF SURGERY VS. WATCHFUL WAITING APPROACH].

INTRODUCTION: Neuroendocrine tumors (NEN) originate from hormone producing cells located in various organs and tissues. NEN are unique tumors in terms of their diverse and particular clinical presentations, growth pattern, location and relatively good prognosis. NEN can be either secreting or non-secreting tumors. The clinical presentation and symptoms are according to the specific hormone produced by the tumor. A non-secreting tumor will eventually cause symptoms that relate to a mass-effect or a metastatic disease. There are various familial and genetic syndromes that are related to NEN. The most common neuroendocrine genetic syndrome is Multiple Endocrine Neoplasia syndrome type 1 (MEN 1). The clinical approach and treatment of NEN are unlike any other cancer. The gold standard management is surgery but unlike other cancerous diseases, surgical intervention is also indicated in cases of metastatic disease. There are several surgical approaches, and they all depend on tumor size, location, grade, stage, lymph node involvement, remote metastases and patients' age and comorbidities. Besides surgery, some cases are also treated with systemic therapies such as Somatostatin analogues, chemotherapy, immunotherapies, targeted therapies and occasionally radiation therapy is used. In the last decade there is a significant increase in the number of patients diagnosed with small non-secreting pancreatic tumors (PNET) due to advanced imaging techniques and diagnostic tools. This incidental increase is the reason for the emerging dilemma of whether to operate or merely conduct a watchful waiting policy. Small non-secreting tumors are commonly not considered malignant and thus the question is if surgery is always the right approach. The benefits of surgery must be carefully considered against the potential damage that may occur during these complex and radical procedures. Moreover, new and progressive systemic pharmacological therapies are now available to efficiently suppress tumor hormonal secretion. Recent studies have challenged surgery as the only treatment of choice, and in some cases suggest conservative treatment and follow up. The aim of this present literature review is to describe PNET diagnostic tools and evaluation, and to examine the different approaches of PNET treatment.

Hand-assisted Laparoscopic Surgery for Colorectal Liver Metastasis: Analysis of Short-term and Long-term Results.

BACKGROUND: There is scant data regarding the outcomes of hand-assisted laparoscopic surgery (HALS) for colorectal liver metastasis (CRLM). The aim of this study is to report our experience and analyze the short-term and long-term results. MATERIALS AND METHODS: Retrospective study of patients undergoing HALS for CRLM in 2 university affiliated medical centers. RESULTS: Two hundred and thirty-eight liver procedures were performed on 145 patients including 205 parenchymal sparing resections and 33 anatomic resections. The median number of metastases was 1 (range: 1 to 8), 38 patients (26.2%) had 3 or more metastases, and 41 patients (28.3 had a bi-lobar disease. The tumor size was 20 (2 to 90) mm, and 52 patients (36.6%) had a tumor larger than 30 mm. Nighty-nine patients (67.8%) received neoadjuvant chemotherapy. In 8 patients (5.5%) the laparoscopic liver resection was combined with ablation, and 16 patients (11%) underwent a synchronous resection of colorectal cancer. The median operative time, blood loss during surgery, and postoperative hospital stay were 163 minutes, 300 mL, and 4 days, respectively. The median modified Iwate complexity score was 4 (0 to 10) and the conversion rate to open surgery was 5.5%. The overall and major complication rates were 23.8% and 3.6%, respectively. The mortality rate was 0.7%. R0 resections were achieved in 91% of patients. Median overall survival for all the cohort (intend to treat) was 59 months, and the 8- and 10-year overall survival rates were 47.3% and 24.9%, respectively. CONCLUSIONS: This study shows that HALS is a safe and efficacious treatment for selected patients with CRLM.

Hazardous Postoperative Outcomes of Unexpected COVID-19 Infected Patients: A Call for Global Consideration of Sampling all Asymptomatic Patients Before Surgical Treatment.

BACKGROUND: In December 2019, a novel coronavirus was identified as the cause of many pneumonia cases in China and eventually declared as a pandemic as the virus spread globally. Few reports were published on the outcome of surgical procedures in diagnosed COVID-19 patients and even fewer on the surgical outcomes of asymptomatic undiagnosed COVID-19 surgical patients. We aimed to review all published data regarding surgical outcomes of preoperatively asymptomatic untested coronavirus disease 2019 (COVID-19) patients. METHODS: This report is a review on the perioperative period in COVID-19 patients who were preoperatively asymptomatic and not tested for COVID-19. Searches were conducted in PubMed April 4th, 2020. All publications, of any design, were considered for inclusion. RESULTS: Four reports were identified through our literature search, comprising 64 COVID-19 carriers, of them 51 were diagnosed only in the postoperative period. Synthesis of these reports, concerning the postoperative outcomes of patients diagnosed with COVID-19 during the perioperative period, suggested a 14/51 (27.5%) postoperative mortality rate and severe mostly pulmonic complications, as well as medical staff exposure and transmission. CONCLUSIONS: COVID-19 may have potential hazardous implications on the perioperative course. Our review presents results of unacceptable mortality rate and a high rate of severe complications. These observations warrant further well-designed studies, yet we believe it is time for a global consideration of sampling all asymptomatic patients before surgical treatment.

Hand-assisted Laparoscopic Repeat Hepatectomy for Secondary Liver Neoplasm.

BACKGROUND: Hand-assisted laparoscopic surgery is a widely accepted alternative to an open approach. The use of this technique in repeat liver resection is limited due to technical difficulties caused by postsurgical adhesions. We aimed to assess the feasibility and safety of hand-assisted laparoscopic repeat hepatectomy (HALRH). MATERIALS AND METHODS: This was a retrospective study of the medical files of patients who had undergone HALRH between 2010 and 2017 in 2 university-affiliated medical centers. RESULTS: Sixteen patients with repeat hepatectomy were included with a median age of 67.5 years. The first liver resection was a traditional laparotomy for 9 patients and hand-assisted laparoscopic surgery for 7 patients. The conversion rate to open surgery was 6%. The median operative time, blood loss during surgery, and postoperative hospital stay were 166 minutes, 400 mL, and 7 days, respectively. R0 resections were achieved in 88% of patients. The median number of tumors and tumor size were 1 and of 25 mm, respectively. There were no mortalities or major complications postoperatively. For patients with colorectal liver metastases, the median follow-up and overall survival were 21 and 43 months, respectively. CONCLUSION: The findings suggest HALRH to be safe and feasible. Future ERAS guidelines should evaluate this approach for liver surgery.

Laparoscopic hand-assisted liver resection for tumours in the left lateral section.

CONTEXT: The role of the laparoscopic left lateral sectionectomy (LLLS) is debatable, and Level-1 data are lacking. AIMS: The aim of the study is to evaluate the feasibility and safety of this approach. SETTINGS AND DESIGN: This was a retrospective study. SUBJECTS AND METHODS: From 2007 to 2014, patients undergoing LLLS were identified from two institutions. STATISTICAL ANALYSIS USED: Continuous variables were compared between groups with Student's t-test or Mann-Whitney test, as appropriate by type of distribution. Categorical variables were compared with Chi-square or Fisher's exact test, depending on the number of observations. RESULTS: Thirty-eight patients were included in the study. The mean age was 63.5 + 13 years (range, 31-89), and the mean number of tumours was 1.7 + 1.5. Eleven (29%) patients underwent LLS combined with an additional liver resection (combined resections group). The mean duration of the operation and the mean estimated blood loss were significantly decreased in the LLS group compared to the combined resection group (101 + 71 min vs. 208 + 98 min and 216 + 217 ml vs. 450 + 223 ml;P < 0.05 for both, respectively). The major complications rate was 8% and no mortality occurred. CONCLUSIONS: In a subset of carefully selected cases, LLLS may provide the benefits of laparoscopy. This does not appear to compromise perioperative morbidity rates. We believe that this approach may serve as a training platform for surgical trainees.

[INTRAOPERATIVE RADIOTHERAPY (IORT) IN EARLY BREAST CANCER - 500 PATIENTS, ONE CENTER'S EXPERIENCE].

AIMS: To present our Institute's experience with intraoperative radiotherapy in this selected population by collecting and analyzing clinical data, including long-term follow-up. BACKGROUND: Breast-conserving therapy is the standard treatment for early-stage breast cancer. The treatment includes tumor resection and a whole breast irradiation. Intraoperative radiotherapy is a single dose of irradiation given to the tumor bed immediately after it is removed. This treatment is suitable for a selected population of patients with early stage breast cancer, which constitutes about 20% of all breast cancer patients and is supposed to replace the standard whole breast radiation treatment. METHODS: Between the years 2006-2017, 737 women with early breast cancer were treated in Carmel Medical Center with intraoperative radiotherapy. We herein report the results of the first 500 patients who were treated until 2015. RESULTS: In 13.8% of the patients, additional breast treatment was recommended due to poor pathological characteristics of the disease in final pathological examination. During a median follow-up period of 74 months (1-136), recurrence was observed in 22 patients (4.4%), and in 7 patients (1.4%) recurrence was observed in regional lymph nodes; 13 patients (2.6%) developed metastatic disease. Risk factors for regional recurrence were identified: tumor size greater than 2 cm, lack of adjuvant therapy and poor genetic profile of the disease. CONCLUSIONS: Intraoperative radiotherapy is feasible and may offer an alternative to the standard whole breast radiotherapy, in low risk early breast cancer patients. The patients should be selected according to known risk factors.

Effect of N-Acetylserotonin on TLR-4 and MyD88 Expression during Intestinal Ischemia-Reperfusion in a Rat Model.

BACKGROUND: Accumulating evidence indicates that changes in intestinal toll-like receptors (TLRs) precede histological injury in a rodent model of necrotizing enterocolitis. N-acetylserotonin (NAS) is a naturally occurring chemical intermediate in the biosynthesis of melatonin. A recent study has shown that treatment with NAS prevents gut mucosal damage and inhibits programmed cell death following intestinal ischemia-reperfusion (IR). The objective of this study was to determine the effects of NAS on TLR-4, myeloid differentiation factor 88 (Myd88), and TNF-α receptor-associated factor 6 (TRAF6) expression in intestinal mucosa following intestinal IR in a rat. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomly assigned to one of the four experimental groups: 1) Sham rats underwent laparotomy; 2) Sham-NAS rats underwent laparotomy and were treated with intraperitoneal (IP) NAS (20 mg/kg); 3) IR rats underwent occlusion of both superior mesenteric artery and portal vein for 20 minutes followed by 48 hours of reperfusion; and 4) IR-NAS rats underwent IR and were treated with IP NAS immediately before abdominal closure. Intestinal structural changes, mucosal TLR-4, MyD88, and TRAF6 mucosal gene, and protein expression were examined using real-time PCR, Western blot, and immunohistochemistry. RESULTS: Significant mucosal damage in IR rats was accompanied by a significant upregulation of TLR-4, MyD88, and TRAF6 gene and protein expression in intestinal mucosa compared with control animals. The administration of NAS decreased the intestinal injury score, inhibited cell apoptosis, and significantly reduced the expression of TLR-4, MyD88, and TRAF6. CONCLUSION: Treatment with NAS is associated with downregulation of TLR-4, MyD88, and TRAF6 expression along with a concomitant decrease in intestinal mucosal injury caused by intestinal IR in a rat.

Sonic hedgehog signaling controls gut epithelium homeostasis following intestinal ischemia-reperfusion in a rat.

PURPOSE: One of the major regulators of gastrointestinal tract development is the hedgehog signaling pathway. The purpose of this study was to evaluate the role of sonic hedgehog (SHh) signaling 24 and 48 h following intestinal ischemia-reperfusion (IR) in a rat. MATERIALS AND METHODS: Male rats were divided into four experimental groups: (1) Sham-24 h rats underwent laparotomy and were sacrificed after 24 h, (2) Sham-48h rats underwent laparotomy and were sacrificed after 48 h, (3) IR-24h rats underwent occlusion of both superior mesenteric artery and portal vein for 20 min followed by 24 h of reperfusion, and (4) IR-48 h rats underwent ischemia for 20 min followed by 48 h of reperfusion. Intestinal structural changes, enterocyte proliferation and enterocyte apoptosis were determined by immunohistochemistry 24 and 48 h following IR. SHh-related genes and protein expression were determined using real-time PCR, Western blot and immunohistochemistry. RESULTS: IR-24 rats demonstrated a significant decrease in Shh, Ihh, GIL and Ptch2 mRNA in jejunum and ileum compared to Sham-24 animals that was accompanied by a significant decrease in the number of SHH-positive cells (Immunohistochemistry) in jejunum (2.5-fold decrease) and ileum (37%). After 48 h, IR rats demonstrated a significant increase in Dhh, Ihh, Gil and PTCH2 mRNA in jejunum as well as in Dhh, Ihh, SMO, GIL, PTCH2 mRNA in ileum compared to IR-24 animals that was coincided with increased number of SHH-positive cells in jejunum (2.6-fold increase) and ileum (1.4-fold increase). CONCLUSIONS: 24 h following intestinal IR, inhibited cell turnover was associated with inhibited SHh signaling pathway. Signs of intestinal recovery appeared 48 h after IR and were correlated with increase in SHh signaling pathway activity.

Oral Bisphosphonates and Improved Survival of Breast Cancer.

Purpose: Bisphosphonates are used for treatment or prevention of osteoporosis and of bone metastases. The use of oral bisphosphonates was suggested to be associated with reduced risk of developing breast cancer, and their positive influence on breast cancer survival was only demonstrated with third-generation bisphosphonates. We studied the association of use of oral bisphosphonates after breast cancer diagnosis on overall and breast cancer survival.Experimental Design: A nested case-control analysis was performed using data from the population-based Breast Cancer in Northern Israel Study (BCINIS). Participants were postmenopausal women with newly diagnosed breast cancer insured by Clalit. Use of second-generation bisphosphonates (alendronate and/or risedronate) was identified using computerized prescription records. The analysis was restricted to women who did not use bisphosphonates prior to diagnosis.Results: In a cohort of 3,731 postmenopausal women with breast cancer, followed up for an average of 70 months, there were 799 cases of death which were matched to 15,915 control periods of living breast cancer cases. Use of bisphosphonates after diagnosis for at least 18 months was significantly more common among survivors than among their matched controls who died, adjusted for tumor stage/grade (overall survival: OR = 0.63, 0.41-0.96, P = 0.03; breast cancer-specific survival: OR = 0.28, 0.09-0.91, P = 0.035). A similar advantageous effect, but statistically underpowered, was found in estrogen receptor (ER)-positive, ER-negative, and HER2neu-positive tumors.Conclusions: The use of oral bisphosphonates, by postmenopausal, probably osteoporotic, women initiated after diagnosis of breast cancer was associated with a significant improvement in overall and breast-specific odds of survival. Clin Cancer Res; 23(7); 1684-9. ©2016 AACR.

Effect of Chelerythrine on Intestinal Cell Turnover following Intestinal Ischemia-Reperfusion Injury in a Rat Model.

Background Chelerythrine (CHE) is a benzophenanthridine alkaloid that is a potent, selective, and cell-permeable protein kinase C inhibitor. The purpose of the present study was to examine the effect of CHE on intestinal recovery and enterocyte turnover after intestinal ischemia-reperfusion (IR) injury in rats. Methods Male Sprague-Dawley rats were divided into four experimental groups: (1) sham rats underwent laparotomy, (2) sham-CHE rats underwent laparotomy and were treated with intraperitoneal CHE; (3) IR-rats underwent occlusion of both superior mesenteric artery and portal vein for 30 minutes followed by 48 hours of reperfusion, and (4) IR-CHE rats underwent IR and were treated with intraperitoneal CHE immediately before abdominal closure. Intestinal structural changes, Park injury score, enterocyte proliferation, and enterocyte apoptosis were determined 24 hours following IR. The expression of Bax, Bcl-2, p-ERK, and caspase-3 in the intestinal mucosa was determined using real Western blot and immunohistochemistry. Results Treatment with CHE resulted in a significant decrease in Park injury score in jejunum (threefold decrease) and ileum (twofold decrease), and parallel increase in mucosal weight in jejunum and ileum, villus height in jejunum and ileum, and crypt depth in ileum compared with IR animals. IR-CHE rats also experienced a significantly lower apoptotic index in jejunum and ileum, which was accompanied by a lower Bax/Bcl2 ratio compared with IR animals. Conclusions Treatment with CHE inhibits programmed cell death and prevents intestinal mucosal damage following intestinal IR in a rat.

Short-term complications of intra-operative radiotherapy for early breast cancer.

INTRODUCTION: IORT is becoming an accepted radiotherapy technique for treatment of early breast cancer. Data regarding the early complications of breast IORT are lacking. OBJECTIVES: Assess the nature and risk factors for early complications of breast conserving surgery (BCS) and intraoperative radiotherapy (IORT) with INTRABEAM®. METHODS: IORT with INTRABEAM® was administered to breast cancer patients in Carmel Medical Center as part of an institutional clinical registry project. Three hundred and ninety five patients treated during 2006-2013 were included. Clinical and treatment data and data regarding complications documented within 1 year of surgery were collected. The association between clinical and treatment variables and risk of complications was assessed. RESULTS: Complications were documented in 108 (27.3%) of patients. Grade III or IV complications were found in 5% of patients. Infections were diagnosed in 43 (10.8%) patients, seroma in 40 (10.1%), wound dehiscence in 32 (8.1%), and bleeding and hematomas in 11(2.8%). Two patients had a small size skin necrosis. Sixteen patients with a seroma had a secondary complication. All complications resolved. Diabetes mellitus and use of anticoagulants were associated with an increased risk of wound dehiscence and bleeding, respectively. CONCLUSIONS: IORT for breast cancer is safe in appropriately selected patients. Careful surgical technique and postoperative care is prudent. J. Surg. Oncol. 2016;113:370-373. © 2016 Wiley Periodicals, Inc.

Clinical and Pathological Characteristics of Incidental Diagnostic Early Occult Malignancy After Risk-Reducing Salpingo-Oophorectomy in BRCA Mutation Carriers.

OBJECTIVE: Carriers of familial BRCA mutations are at high risk of early development of ovarian tubal or peritoneal cancers. The definite preventative treatment for these cases is early, risk-reducing, bilateral salpingo-oophorectomy (BSO). The aims of the study were to describe the incidence and source of early occult malignancy after risk-reducing salpingo-oophorectomy in carriers of Ashkenazi Jewish BRCA mutations and to characterize the clinical and pathological features of this unique population. METHODS: Data were collected retrospectively regarding women who underwent BSO in our gynecologic oncology unit from January 2002 through July 2012, after a positive test for a BRCA1 or BRCA2 mutation. RESULTS: The following 92 cases of BRCA mutations were included: 53 BRCA1, 37 BRCA2, and 2 with both mutations. After risk-reducing salpingo-oophorectomy, 5 (5.4%) of the patients were found to have early occult adnexal malignancy upon pathology study. All 5 had the BRCA1 185 del-AG mutation. Three of the 5 malignancies originated from the ovaries and 2 in the fallopian tubes with no involvement of the ovaries. CONCLUSIONS: A 5.4% incidence of early occult malignancy in adnexal pathology of BSO was found in carriers of Ashkenazi Jewish BRCA mutations. Two cases with malignant origins within the fallopian tube, while sparing the ovaries in their entirety, support the fallopian tubes as the originating organ for some ovarian or peritoneal malignancies in BRCA mutation carriers.

Effect of N-Acetylserotonin on Intestinal Recovery Following Intestinal Ischemia-Reperfusion Injury in a Rat.

OBJECTIVE: N-acetylserotonin (NAS) is a naturally occurring chemical intermediate in the biosynthesis of melatonin. Extensive studies in various experimental models have established that treatment with NAS significantly protects heart and kidney injury from ischemia-reperfusion (IR). The purpose of the present study was to examine the effect of NAS on intestinal recovery and enterocyte turnover after intestinal IR injury in rats. METHODS: Male Sprague-Dawley rats were divided into four experimental groups: (1) Sham rats underwent laparotomy, (2) sham-NAS rats underwent laparotomy and were treated with intraperitoneal (IP) NAS (20 mg/kg); (3) IR rats underwent occlusion of both superior mesenteric artery and portal vein for 30 minutes, followed by 48 hours of reperfusion, and (4) IR-NAS rats underwent IR and were treated with IP NAS (20 mg/kg) immediately before abdominal closure. Intestinal structural changes, Park injury score, enterocyte proliferation, and enterocyte apoptosis were determined 24 hours following IR. The expression of Bax, Bcl-2, p-ERK, and caspase-3 in the intestinal mucosa was determined using real-time polymerase chain reaction, Western blot, and immunohistochemistry. A nonparametric Kruskal-Wallis analysis of variance test was used for statistical analysis with p less than 0.05 considered statistically significant. RESULTS: Treatment with NAS resulted in a significant increase in mucosal weight in jejunum and ileum, villus height in the ileum, and crypt depth in jejunum and ileum compared with IR animals. IR-NAS rats also had a significantly proliferation rates as well as a lower apoptotic index in jejunum and ileum which was accompanied by higher Bcl-2 levels compared with IR animals. CONCLUSIONS: Treatment with NAS prevents gut mucosal damage and inhibits programmed cell death following intestinal IR in a rat.

[TURNOVER CAPSULAR FLAPS FOR THE TREATMENT OF IMPENDING EXTRUSION OF SILICONE PROSTHESIS IN RECONSTRUCTED BREASTS].

Pressure necrosis which might be followed by skin necrosis and implant extrusion is a dreaded complication of breast reconstructive surgery. Over the years, several techniques have been introduced to address this challenging problem. We offer a novel surgical technique to confront this perplexing complication. By using the capsule of the implant as a turnover flap, the soft tissue coverage is enhanced thereby decreasing the pressure between the breast prosthesis and the over-laying skin. The technique is simply reproduced, requires no new incisions, and avoids further morbidity to the involved breast reconstructed patient.

[INTRAVENOUS CHEMOTHERAPY VERSUS INTRAPERITONEAL CHEMOTHERAPY IN ADVANCED OVARIAN CANCER: UPDATE ON THE SITUATION WORLDWIDE AND IN ISRAEL].

Ovarian cancer is the second in incidence and the first cause of death. As much as 70% of ovarian cancer patients are diagnosed with advanced disease. The standard treatment of advanced ovarian cancer is a combination of primary optimal debulking (POD) followed by a combined adjuvant chemotherapy treatment. Another optional treatment includes neoadjuvant chemotherapy followed by optimal debulking and then adjuvant chemotherapy. The common adjuvant chemotherapy includes a combination of platinum and taxol compounds given intravenously. Other possible treatments which had been evaluated in the past decades include a combination of chemotherapy given intravenously and intraperitoneally. The rationale behind delivering the chemotherapy intraperitoneally is to provide a much higher concentrations of cytotoxic agents in the peritoneal cavity and to reduce the systemic side effects. A number of randomized trials have shown that the combination of IV and IP chemotherapy entails a survival advantage. Most studies included treatment based on cisplatin treatments with/ without taxol given intravenously versus a combined treatment (intravenously and intraperitoneally) of those agents. An advantage of up to 8 months in disease-free survival and 11 months in overall survival was noted in the IP group. On the other hand, this treatment led to a higher rate of side effects, including abdominal pain, electrolyte imbalance and catheter related complications. Despite the inconsistency in the treatment protocols between the different trials comparing intravenous and intra-peritoneal treatment, one cannot ignore the statistical significance between the groups, for disease-free survival and overall survival. That is why, when addressing patients who completed optimal surgery, one needs to conduct a thorough evaluation regarding the complementary chemotherapy treatment. Due to the broad side effect profile, special notice should be taken as to the patient's age, medical history, and performance status after the primary surgery and her ability to endure an aggressive chemotherapy treatment. By doing so, it will be possible to select the ovarian cancer patients who will benefit he most from combining intravenous and intraperitoneal treatment.

[OUTCOMES OF HEPATIC, PANCREATIC AND GASTRIC SURGERY IN THE ELDERLY POPULATION: MORBIDITY, MORTALITY AND RESPONSE TO ONCOLOGIC TREATMENT].

INTRODUCTION: There is a continuous rise in the proportion of elderly people in the general population. Previously, old age was a contraindication for numerous medical procedures. AIM: To assess the postoperative outcome of elderly patients who underwent major surgery of the liver, pancreas and stomach. MATERIALS AND METHODS: A retrospective analysis of patients aged 75 and older who underwent elective operations for malignant tumors of the stomach, pancreas and liver between January 2005 and December 2009 in the Department of Surgery A, at Carmel Medical Center. RESULTS: Of 258 operations, 80 (31%) were performed on patients older than 75 years; 46 (57.5%) were for males and 34 (42.5%) for females, with a mean age of 79 years. One patient was operated on twice. In 68 Patients (85%) the disease was primary and in 12 (15%) it was metastatic; 28 (35.4%) tumors were in the distal stomach, 13 (16.5%) in the proximal stomach; in the pancreas 13 tumors (16.5%) were in the head and 8 (10.1%) in the body/tail; 17 patients had liver metastases (21.5%1; 68 operations (85%) were performed in an open approach and 12 (15%) laparoscopically. Median hospital stay was 12 (±7.48) days and median ICU stay was 2 (±3.53) days. Median followup was 23 (±23) months. Complete records of 76 patients showed that 33 (43.4%) are alive with no evidence of disease; 12 (15.8%) were alive with stable disease; 25 (32.89%) died of cancer and 6 (7.8%) of other causes. DISCUSSION: These favorable results allow us to offer elderly patients the entire spectrum of surgical and medical procedures without considering advanced age as an absolute contraindication. CONCLUSIONS: Chronological age as a single parameter should not be a contraindication for radical medical treatment.

[Intraoperative radiotherapy (IORT) in early breast cancer].

BACKGROUND: Breast-conservation therapy is widely accepted as an effective treatment option for patients with early stage carcinoma of the breast. The proportion of patients with recurrence after receiving partial breast irradiation is the same as that seen in patients treated with whole breast irradiation. Therefore, the necessity of whole breast irradiation has been questioned, and partial breast irradiation has emerged as a reasonable alternative. METHODS: Since 2006, 468 women with early breast cancer (age > 60 years, T1, infiltrative duct carcinoma and with no clinical or sonographic suspicion of involved axillary lymph nodes) were treated in the Carmel Medical Center with intraoperative radiotherapy, using the INTRABEAM System giving 20 Gy at the tumor bed. We report the cohort of the first 100 patients who have had a follow up period of more than 3 years. RESULTS: The median age was 70 years (range 56-87 years). Twenty four patients had mild to moderate local complications, while nine patients experienced major local complications. Eighteen patients had metastatic involvement of the axillary lymph nodes, and in 16 of them, only one node was involved. Five patients had additional local therapy (one patient underwent mastectomy and four patients received whole breast irradiation). During the follow up period, four ipsilateral breast failures were observed: two new primary tumors (by location and histology) and two local recurrences. CONCLUSIONS: Intraoperative radiotherapy using the INTRABEAM system is feasible and may offer an alternative to whole breast radiotherapy, in low risk early breast cancer patients with a low rate of local recurrence and morbidity. Longer follow up is required in order to evaluate long term results and late toxicity.

Effect of ozone on intestinal recovery following intestinal ischemia-reperfusion injury in a rat.

BACKGROUND: Growing evidence suggests that ozone (O3) protects the host against pathological conditions mediated by reactive oxygen species by increasing the activity of antioxidant enzymes. The purpose of the present study was to examine the effect of O3 on intestinal recovery and enterocyte turnover after intestinal ischemia-reperfusion (IR) injury in rats. METHODS: Male Sprague-Dawley rats were divided into four experimental groups: (1) sham rats underwent laparotomy; (2) sham-O3 rats underwent laparotomy and were treated with an ozone/oxygen mixture intraperitoneally and intraluminally (50 %/50 %); (3) IR rats underwent occlusion of both superior mesenteric artery and portal vein for 20 min followed by 48 h of reperfusion, and (4) IR-O3 rats underwent IR and were treated with an ozone/oxygen mixture similar to group 2. Intestinal structural changes, Park's injury score, enterocyte proliferation and enterocyte apoptosis were determined 48 h following IR. Western blot was used to determine ERK and Bax protein levels. A non-parametric Kruskal-Wallis ANOVA test was used for statistical analysis with p < 0.05 considered statistically significant. RESULTS: Treatment of IR rats with O3 resulted in a significant increase in mucosal weight in jejunum (70 %) and ileum (32 %), mucosal DNA (twofold increase) and protein (35 %) in ileum, villus height and crypt depth in jejunum (61 and 16 %, correspondingly) and ileum (31 and 43 %, correspondingly) compared to IR animals. IR-O3 rats also had a significantly lower intestinal injury score as well as a lower apoptotic index in jejunum and ileum compared and IR animals. A significant increase in cell proliferation rates in IR-O3 animals was accompanied by increased levels of p-ERK protein. CONCLUSIONS: Treatment with ozone prevents intestinal mucosal damage, stimulates cell proliferation and inhibits programmed cell death following intestinal IR in a rat.

Statins, aspirin and risk of venous thromboembolic events in breast cancer patients.

Venous thromboembolic events (VTE's) are associated with decreased survival in breast cancer patients. Studies suggested that statins reduce the risk of VTE's in the general population. Low dose Aspirin reduces risk of VTE's in high risk populations. The Breast Cancer in Northern Israel Study is a case-control study of consecutive breast cancer cases diagnosed in northern Israel and matched controls. The present analysis was limited to cases with breast cancer enrolled in the study. Data was extracted from Clalit Health Services (CHS) database and from computerized pharmacy records. Out of 3,585 patients enrolled, 261 (7.3%) had a VTE during median follow up of 4.2 years. The 1 and 2 year cumulative incidence was 2.64 and 3.65%. 55.7% of patients used statins, predominantly simvastatin (75.8%). 44.5% used aspirin. In multivariate analysis neither statins nor aspirin use was associated with a reduced risk for a VTE. Unadjusted HR for statin and aspirin was 1.461 (1.018-2.096) and 1.293 (0.846-1.976), respectively, and the adjusted HR were 0.86 (0.648-1.14) and 1.013 (0.737-1.392). Results were similar when only simvastatin use was assessed. Metastatic disease, chemotherapy, age, BMI and presence of comorbidities were significantly associated with risk of VTE's. Our study is the first to look at the effect of statins and aspirin on the incidence of VTE's in patients with breast cancer. In our cohort, statin and aspirin use did not decrease the risk for a VTE. Our results might be explained by use of low potency statins (simvastatin and pravastatin) and by alternate mechanisms for VTE formation in patients with cancer.

[Takotsubo cardiomyopathy following surgical intervention for treatment of bowel obstruction].

We report a case of Takotsubo cardiomyopathy [TCM] occurrence in a 75-years-old female after surgical intervention for the treatment of bowel obstruction. Approximately 24 hours after the procedure, the hemodynamic and respiratory status of the patient deteriorated. Marked ECG ST segment elevation, and troponin levels were moderately elevated in a pattern suitable for ST elevation myocardial infarction [MI). Coronary angiogram showed no sign of coronary obstruction, and an angiography of the left ventricle, presented a template of apical ballooning highly suspicious of Takotsubo syndrome.