Laparoscopic colorectal cancer surgery combined with enhanced recovery after surgery protocol (ERAS) reduces the negative impact of sarcopenia on short-term outcomes.

INTRODUCTION: Progressive skeletal muscle loss (sarcopenia) is a negative prognostic factor in patients treated for colorectal cancer. Nevertheless, the clinical impact of those changes in body composition has been analyzed only in patients undergoing open resections. The aim of the study was to assess whether laparoscopy may eliminate the deleterious prognostic impact of sarcopenia and whether the combination with enhanced recovery after surgery (ERAS) protocol may improve postoperative recovery also in sarcopenic patients. METHODS: The study included 124 (73M/51F, mean age 65.9 years) patients undergoing elective laparoscopic colorectal resection for cancer. In all of them 16-item ERAS protocol was applied. The L3 skeletal muscle area identified on a preoperative CT scan was used to calculate skeletal muscle index and assess for sarcopenia and myosteatosis. The entire study group was divided into groups regarding the presence of sarcopenia or myosteatosis. The outcome measures were: length of hospital stay, complication rate and functional recovery parameters. RESULTS: The prevalence of sarcopenia and myosteatosis was 27.4% and 38.7%, respectively. There was no association between the presence of sarcopenia or myosteatosis and postoperative complications. There were also no differences in the length of stay or readmission rates. Functional recovery (time to first flatus, oral diet tolerance and mobilization) was similar regardless of the presence of muscle depletion. CONCLUSIONS: In contrary to traditional surgical approach, laparoscopy can reduce the negative impact of sarcopenia and myosteatosis on treatment results. ERAS protocol does not affect negatively the surgical outcomes in sarcopenic patients, compared to patients without changes in body skeletal mass.

Relationships between obesity, bipolar spectrum features, and personality traits: a case-control study.

OBJECTIVE: Recently there has been widening stream of research on the relationships between obesity and mental disorders. Patients with obesity seem to be prone to developing bipolar spectrum disorders and they present with specific personality traits. The aim of this study was to analyze the associations between obesity, bipolarity features, and personality traits. PATIENTS AND METHODS: A nested case-control study was performed. Patients with obesity constituted the sample of cases (N = 90), and healthy individuals were ascribed to the control group (N = 70). The lifetime presence of bipolarity features was analyzed with the Mood Disorder Questionnaire (MDQ), while personality traits were assessed with the NEO-Five Factor Inventory (NEO-FFI). RESULTS: Bipolarity features were more prevalent in the patients with obesity, as compared to healthy individuals. Patients with obesity had both higher mean value of MDQ score (p = 0.01) and a higher proportion of subjects with MDQ score ≥ 7 points (p = 0.012) as well as lower score on the NEO-FFI openness to experience (p > 0.001), compared to control subjects. Using multivariate model, in patients with obesity, a significant positive correlation between bipolarity and neuroticism, and negative with agreeableness and conscientiousness was established. Such relationship was not observed in control subjects. CONCLUSIONS: In the population of patients with obesity, there is a specific combination between bipolarity and personality traits (high-trait neuroticism, low-trait conscientiousness, and low-trait agreeableness). This may have some consequences for both pharmacological and psychological management of such patients.

The knowledge of Polish medical students about surgical treatment of obesity.

BACKGROUND: Surgical treatment of morbid obesity is becoming an increasingly important approach for the treatment of this condition. However, knowledge about the possibility of surgical procedures among general practitioners is far from satisfactory. The source of the problem might be due to a lack of information about bariatric surgery in university curriculum. METHODS: We assessed the knowledge of students from four Polish medical universities. The survey was conducted among 468 students, in their sixth (final) year of study. The survey included two parts-the first nine questions assessed of the level of the students' knowledge about the methods of surgical treatment of obesity, and the following three questions allowed for an evaluation of the amount of information on metabolic surgery provided to students during surgery courses. RESULTS: The results demonstrate a low level of knowledge on the possibility of applying metabolic surgery to treat morbid obesity. The students themselves expressed a need to improve their knowledge and favorably assessed the proposition of expanding the curriculum to include more information on the subject of metabolic surgery. CONCLUSION: The awareness of surgical treatment for morbid obesity among medical students should be improved. The development of an interesting curriculum that is based on current guidelines should be undertaken.

Induced pluripotent stem cells as a model for diabetes investigation.

Mouse and human induced pluripotent stem cells (iPSCs) may represent a novel approach for modeling diabetes. Taking this into consideration, the aim of this study was to generate and evaluate differentiation potential of iPSCs from lep(db/db) (db/db) mice, the model of diabetes type 2 as well as from patients with Maturity Onset Diabetes of the Young 3 (HNF1A MODY). Murine iPSC colonies from both wild type and db/db mice were positive for markers of pluripotency: Oct3/4A, Nanog, SSEA1, CDy1 and alkaline phosphatase and differentiated in vitro and in vivo into cells originating from three germ layers. However, our results suggest impaired differentiation of db/db cells into endothelial progenitor-like cells expressing CD34 and Tie2 markers and their reduced angiogenic potential. Human control and HNF1A MODY reprogrammed cells also expressed pluripotency markers: OCT3/4A, SSEA4, TRA-1-60, TRA-1-81, formed embryoid bodies (EBs) and differentiated into cells of three germ layers. Additionally, insulin expressing cells were obtained from those partially reprogrammed cells with direct as well as EB-mediated differentiation method. Our findings indicate that disease-specific iPSCs may help to better understand the mechanisms responsible for defective insulin production or vascular dysfunction upon differentiation toward cell types affected by diabetes.

Laparoscopic Surgery In The Treatment of Gastrointestinal Stromal Tumors.

BACKGROUND AND AIMS: Gastrointestinal stromal tumors are rare neoplasms of the gastrointestinal tract. These lesions are characterized by different levels of malignancy. Only radical surgery offers a chance of curing the disease. The aim of this study is to present the results of gastrointestinal stromal tumor treatment with minimally invasive surgery. MATERIAL AND METHODS: The study group included 27 patients operated laparoscopically on for gastrointestinal stromal tumor with laparoscopic surgery between September 2009 and December 2013. The most common location of the tumor was the stomach (21 patients, 77.8%) and the small intestine (4 patients, 14.8%). We analyzed early surgery results, the number and character of complications, lengths of hospital stays, histological types of the removed tumors, and long-term results of treatment. RESULTS: There was no need for conversion to open surgery in any patient from the study group. Post-surgery complications occurred in 2 patients (7.4%). The median duration of the hospital stay was 4.5 days; none of the patients had to be readmitted to the hospital in the first 30 days after the procedure. In 26 out of 27 patients, microscopic examination confirmed the radicality of the surgical procedure (R0 resection). The mean size of the removed lesions was 4.1 cm. Using the Joensuu malignancy classification model, it was established that in 6 (22.2%) patients gastrointestinal stromal tumor was characterized by a very low level of malignancy, in 11 patients (40.7%) a low level, in 4 (14.9%) a medium level, and in 6 (22.2%) a high level. The average duration of follow-up was 13 months. During the observation period, there was no recurrence of the disease. CONCLUSION: Minimally invasive surgery in the treatment of gastrointestinal stromal tumors is possible and allows for satisfactory results both in terms of the postoperative course and the oncological quality of the procedure.

Mechanical Bowel Obstruction--Changes in Aetiology over the Past 145 Years: A Single Centre Retrospective Cohort Study.

INTRODUCTION: Mechanical bowel obstruction (MBO) remains one of the most common abdominal surgical emergencies. The aetiology of MBO depends on the population demographics and period of time in which a given population was studied. We are presenting the results of an analysis covering 145 years of observations based on patients operated in our department. METHODS: The single centre retrospective analysis included 1825 patients with MBO. They were divided into 4 groups depending on the years in which they were treated : group 1 (1868-1898), group 2 (1956-1970), group 3 (1987-1999), group 4 (2000-2013). The analysis covered the sex distribution, the mean age of patients versus the life expectancy and changes in MBO aetiology in every period. RESULTS: We noticed an increase in the mean age and the growing divergence between life expectancy. Additionally, an increasing percentage of women were observed. There were also significant changes in the aetiology. An increase in MBO caused by cancer was observed. The rate of strangulated hernias doubled in the second period of time, and then it gradually decreased. Intestinal volvulus was common in the first period and became one of the rarest causes of MBO in the subsequent periods. MBO due to adhesions remained at the same level. It became, however, the most common cause in the last period. CONCLUSIONS: Within nearly 150 years significant changes occurred in the demographics and aetiology of MBO. Currently, the most common cause is peritoneal adhesions after previous surgeries. Although our results represent a single centre experience, they may reflect changing patterns in MBO in the Polish population over time.

Short hospital stays after laparoscopic gastric surgery under an Enhanced Recovery After Surgery (ERAS) pathway: experience at a single center.

INTRODUCTION: Recently, first reports on benefits from Enhanced Recovery After Surgery (ERAS) pathway in patients undergoing gastric surgery have appeared. It seems that maximal reduction of unfavorable surgery-induced trauma in patients with gastric malignancy via ERAS protocol combined with minimally invasive techniques can improve outcomes. OBJECTIVE: The aim of this study was to determine the influence of laparoscopic surgery and ERAS protocol in oncological gastric surgery on early outcomes. MATERIALS AND METHODS: Prospective analysis involved 28 patients (18 female and 10 male) with gastric malignancy who underwent laparoscopic gastric resection between 2009 and 2013. Gastric tumors (gastrointestinal stromal tumors or adenocarcinoma) were the indication for the surgery. A total of 17 patients underwent laparoscopic local excision, and 11 patients with adenocarcinoma or multiple neuroendocrine tumors underwent laparoscopic D2 total gastrectomy. Perioperative care was based on ERAS principles. Length of hospital stay, postoperative course, perioperative complications, and readmission rates were analyzed. RESULTS: There was one conversion in the gastrectomy group. All patients were mobilized on the day of surgery. Oral fluids were introduced on day 0 and were well tolerated. Full hospital diet was started on day 2 in all patients, but was well tolerated in only 18 of them. One postoperative complication requiring reoperation was noted. The length of stay after gastrectomy and gastric wedge resection was 4.6 (2-6) and 3.3 (2-6) days, respectively. No readmissions were noted in the entire group. CONCLUSIONS: The implementation of ERAS protocol to clinical practice in combination with laparoscopy in patients with gastric tumors can result in improved postoperative care quality, shortening of hospital stay, and quicker return to normal activity.

Validation of the Joensuu risk criteria for primary resectable gastrointestinal stromal tumour - the impact of tumour rupture on patient outcomes.

BACKGROUND: Approval of imatinib for adjuvant treatment of gastrointestinal stromal tumours (GIST) raised discussion about accuracy of prognostic factors in GIST and the clinical significance of the available risk stratification criteria. METHODS: We studied the influence of a new modification of the NIH Consensus Criteria (the Joensuu risk criteria), NCCN-AFIP criteria, and several clinicopathological factors, including tumour rupture, on relapse-free survival (RFS) in a prospectively collected tumour registry series consisting of 640 consecutive patients with primary, resectable, CD117-immunopositive GIST. The median follow-up time after tumour resection was 39 months. None of the patients received adjuvant imatinib. RESULTS: The median RFS time after surgery was 50 months. In univariable analyses, high Joensuu risk group, tumour mitotic count >5/50 HPF, size >5 cm, non-gastric location, tumour rupture (7% of cases; P = 0.0014) and male gender had adverse influence on RFS. In a multivariable analysis mitotic count >5/50HPF, tumour size >5 cm and non-gastric location were independent adverse prognostic factors. Forty, 151, 86 and 348 patients were assigned according to the Joensuu criteria to very low, low, intermediate and high risk groups and had 5-year RFS of 94%, 94%, 86% and 29%, respectively. CONCLUSION: The Joensuu criteria, which include 4 prognostic factors (tumour size, site, mitotic count and rupture) and 3 categories for the mitotic count, were found to be a reliable tool for assessing prognosis of operable GIST. The Joensuu criteria identified particularly well high risk patients, who are likely the proper candidates for adjuvant therapy.

SILS (single incision laparoscopic surgery) - new surgical approach to peritoneal cavity.

PURPOSE: The objective of the modern surgery is not only to perform surgical procedures aiming to improve the health condition of the patient, but whenever possible to use minimally invasive approach and to ensure the satisfying cosmetic result. During the last years we can observe an intense development of surgical technique minimizing the access to peritoneal cavity to just one small incision, most frequently localized in the umbilicus. MATERIAL/METHODS: Between October 2009 and May 2010 an overall number of 34 laparoscopic procedures through a single abdominal wall incision were performed at the 2nd Department of Surgery, Jagiellonian University, Medical College in Krakow. There were 28 women and 6 men in the study group ranging in age from 19 - 76 years. Among indications for surgery there were: symptomatic gallbladder stones (21 patients), adrenal gland tumours (8 patients), ITP - Immune Thromocytopenic Purpura (2 patients), appendicitis (2 patients) and splenic cyst (one patient). RESULTS: There were 31 out of 34 procedures completed with pure Single Incision Laparoscopic Surgery (SILS) technique as intended preoperatively without any intraoperative complications. In 3 patients additional trocars were needed for safe continuation of the procedure. There were no intraoperative complications. The mean operating time was 82 minutes ranging from 25 minutes (appendectomy) to 180 minutes (right adrenalectomy). Mean intraoperative blood loss was 0 - 30 ccm. CONCLUSIONS: SILS surgical procedures constitute the next step in the development of minimally invasive surgery. In the hands of experienced surgeon this particular technique may constitute a safe alternative for classical laparoscopy.

Cyclooxygenase-2 (COX-2) is the key event in pathophysiology of Barrett's esophagus. Lesson from experimental animal model and human subjects.

Mixed reflux of the gastroduodenal contents induces the esophageal mucosal damage and inflammation progressing chronic esophagitis and premalignant Barrett's esophagus (BE). The role of cyclooxygenase-2 (COX-2) and chronic inflammation in the progression of BE toward adenocarcinoma of the esophagus has not been extensively studied in experimental models of BE in animals and in human subjects. We evaluated the expression of COX-2 in rat model of BE and examined the usefulness of COX-2 expression in determining the risk of malignant transformation in patients with BE treated with argon plasma coagulation (APC) that allows for effective ablation of metaplastic mucosa (group A) without or with proton pump inhibitors (PPI). In addition, the group B of patients was subjected to laparoscopic Nissen's fundoplication and group K that served as control, received PPI treatment only. Expression of COX-2 was evaluated in fresh-frozen biopsy specimens obtained from the distal esophagus in all 60 patients before and 12 months after treatment. In experimental studies, eighty rats were surgically prepared with esophagogastroduodenal anastomosis (EGDA) resulting in chronic esophagitis. At 4 months, the esophageal damage in EGDA rats was evaluated by macroscopic and histological index score, the plasma IL-1beta and TNF-alpha levels was determined by ELISA and the mucosal expression of COX-2 mRNA and COX-2 protein were assessed by RT-PCR and Western Blot, respectively. Chronic esophagitis was developed in all EGDA animals followed by the rise in the plasma TNF-alpha and IL-1beta levels. Histology revealed extensive esophageal ulcerations with development of columnar epithelium, formation of mucus glands in squamous epithelium, intestinal metaplasia distant to anastomosis consisting of goblet cells, infiltration of inflammatory cells including plasma cells and lymphocytes. COX-2 mRNA was absent in the esophageal mucosa of sham-control animals but strongly upregulated in metaplastic Barrett's epithelium. In BE patients, the overexpression of COX-2 was documented in patients with dysplasia. After APC (group A) or Nissen's fundoplication (group B), the expression of COX-2 mRNA was markedly reduced and these effects were positively correlated with histopathological findings. Controls failed to show significant alterations in COX-2 expression. We conclude that 1) EGDA rats serve as the suitable model of the chronic esophagitis by the gastrointestinal refluxate resembling many features of those observed in human Barrett's esophagus, as confirmed by severe morphology changes, excessive release of proinflammatory cytokines TNF-alpha and IL-1beta and overexpression of COX-2, and 2) the significant correlation of the degree of COX-2 overexpression with histopathological findings indicates the usefulness of this inducible biomarker as a valuable indicator of the risk of malignant transformation in patients with BE.

IL-6 and IL-8 responses of colorectal cancer in vivo and in vitro cancer cells subjected to simvastatin.

Recent investigations suggest that proinflammatory cytokines such as IL-6 and IL-8 are involved in the development of colorectal cancer (CRC), whereas statins, primarily used to decrease high levels of blood cholesterol, exhibit pleiotropic effects on carcinogenesis. In the present study we compared the expression of IL-8 and IL-6 in tissue samples of tumor and adjacent normal colon mucosa obtained from patients with advanced colorectal cancer (CRC). The analysis of mRNAs expression for these proinflammatory cytokines determined by RT-PCR showed a higher level of IL-8-mRNA in tumor tissue than in normal mucosa, while IL-6 was similarly expressed in tumor and normal tissue. The mean values of serum levels of both IL-6 and IL-8 were significantly higher in CRC patients than in healthy volunteers. Surgical removal of the tumor resulted in a prompt decrease of serum level of IL-8 already on the third day, whereas IL-6 level was transiently increased to become lower only after 7-10 days. Treatment of CRC with simvastatin (80 mg/day for 14 days) led to a significant decrease of serum IL-6, while the IL-8 level was less affected. The in vitro experiments on colorectal cancer-derived cell lines (HT-29 and Caco-2) demonstrated that application of simvastatin decreased generation of both IL-6 and IL-8. The differences in response of serum levels of IL-6 and IL-8 after tumor removal and treatment with simvastatin are novel observations suggesting distinct pathological roles of the two cytokines in CRC development. We conclude that 1) colorectal carcinogenesis is accompanied by increased synthesis and release of proinflammatory cytokines such as IL-6 and IL-8; 2) simvastatin therapy results in a decrease in serum level of proinflammatory cytokines, especially IL-6 in CRC and 3) simvastatin inhibits release of IL-8 and IL-6 from colorectal cell lines.