Slobodan Krstic

Clinical relevance of IL-6 gene polymorphism in severely injured patients

In polytrauma, injuries that may be surgically treated under regular circumstances due to a systemic inflammatory response become life-threatening. The inflammatory response involves a complex pattern of humoral and cellular responses and the expression of related factors is thought to be governed by genetic variations. This aim of this paper is to examine the influence of interleukin (IL) 6 single nucleotide polymorphism (SNP) -174C/G and -596G/A on the treatment outcome in severely injured patients. Forty-seven severely injured patients were included in this study. Patients were assigned an Injury Severity Score. Blood samples were drawn within 24 h after admission (designated day 1) and on subsequent days (24, 48, 72 hours and 7 days) of hospitalization. The IL-6 levels were determined through ELISA technique. Polymorphisms were analyzed by a method of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR). Among subjects with different outcomes, no statistically relevant difference was found with regards to the gene IL-6 SNP-174G/C polymorphism. More than a half of subjects who died had the SNP-174G/C polymorphism, while this polymorphism was represented in a slightly lower number in survivors. The incidence of subjects without polymorphism and those with heterozygous and homozygous gene IL-6 SNP-596G/A polymorphism did not present statistically significant variations between survivors and those who died. The levels of IL-6 over the observation period did not present any statistically relevant difference among subjects without the IL-6 SNP-174 or IL- 6 SNP -596 gene polymorphism and those who had either a heterozygous or a homozygous polymorphism.

Capsule endoscopy is useful diagnostic tool for diagnosing Meckel's diverticulum.

Objective Meckel’s diverticulum (MD) is the most common congenital anomaly of the gastrointestinal tract. Although a majority of patients remain asymptomatic, complications may occur in a subset of patients. MD is a rare cause of gastrointestinal bleeding (GIB) in adults. We aimed to clarify the possible role of capsule endoscopy (CE) in the identification of Meckel’s diverticulum. Patients and methods From October 2004 to December 2010, 157 CEs were performed (83 male individuals, mean age 51±20 years; range 3–83 years) for obscure GIB. Before CE, all patients underwent nonconclusive upper and lower endoscopy at least two times and barium follow-through. Results CE identified the source of bleeding in 70/157 patients (44.6%). MD was diagnosed in 13/70 (18.6%) patients (11 male individuals, mean age 35±20 years, range, 3–69 years) after CE. Nine patients presented with obscure overt and four with obscure occult bleeding. The mean duration of obscure GIB history was 13 months (range 1–72 months). The mean hemoglobin concentration at the time of the procedure was 115±12 g/l. The findings of MD on CE were double lumen sign (13/13), visible blood (7/13), and diaphragm sign (6/13). All patients were operated upon, and MD histologically verified in 11. In two patients CE was false-positive and in two patients, false-negative. Capsule endoscopy had a positive predictive value of 84.6% for the diagnosis of MD. Conclusion MD should be considered in the differential diagnosis of obscure GIB in adults. CE is an effective and promising modality for diagnosing MD in patients with obscure GIB.

Acute Appendicitis: Still a Surgical Disease? Results from a Propensity Score-Based Outcome Analysis of Conservative Versus Surgical Management from a Prospective Database

Dear Editor, We read with great care and interest the article on acute appendicitis treatment modalities by Allievi et al. [1]. in the June 2017 issue of World Journal of Surgery. First of all, we wish to congratulate the authors on this scientific report and on their dedication to better understanding of this very significant disease and its treatment modalities. This was a study with prospective data collection, which included 462 patients who underwent operative and conservative treatment for acute appendicitis. In order to reduce bias arising from characteristics of patients, propensity score-based matching was implemented. However, we have some concerns regarding the exact data on complications after surgical treatment. We feel that more precise data of complications (wound infection and dehiscence, postoperative ileus and incisional hernia) could be very useful, i.e., the type of incision that was performed (Median or McBurney).Also, we think that it would be very useful to know if these complications were more frequent in the group of patients operated by non-experienced surgeons and in the group of patient with postponed surgical intervention (up to 72 h as stated in the paper). In the multicentre prospective, cohort study Bhangu et al. [2] revised 2510 patients and showed that after 48 h the risk of surgical site infection and 30-day adverse events both increased—adjusted ORs 2.24 (P = 0.039) and 1.71 (P = 0.024), respectively. The very same question arose on Consensus Conference on acute appendicitis organized by World Society of Emergency Surgery held in Jerusalem in 2015. In the absence of level 1 evidence, conclusion was that short delay of emergency surgery up to 12–24 h is not linked to poorer outcome and that delays should be minimized in order to decrease costs, enable recovery and control pain [3]. Bearing this in mind, we think that it would be very useful to know if the complications after surgical intervention were more frequent in the group of patients with postponed operative treatment (48–72 h after patients’ admission). According to recent studies [4, 5] usage of antibiotics is linked to Clostridium difficile infection and diarrhea associated with it. Antibiotic therapy is the principal risk factor for Clostridium difficile infection [4]. Furthermore, four different types of probiotic were found to be effective for primary prevention of Clostridium difficile infection [5]. According to these data, we think that the standard usage of probiotic could be appropriate in patients treated conservatively. Also, we feel that diarrheal syndrome should be taken into account as one of the complications of conservative treatment and antibiotics admission in general. We hope that these additional data would give more accurate directives in treating patients with acute appendicitis, in order to define the best approach and therapeutic strategy.

Identification of Recurrence: Predictive Indicators in Stage I Colorectal Cancer

Dear Editor, We read with great interest the paper by Lee et al. [1] on predictive indicators in stage I of colorectal cancer in the November 2016 issue of World Journal of Surgery. At this place, we wish to offer our gratitude and congratulate the authors for their tremendous work and efforts in determining predictive indicators and risk factors for colon cancer recurrence after radical surgery. This was a retrospective analysis which included 860 patients who underwent curative surgery for stage I colorectal cancer. The authors wanted to evaluate the clinicopathologic characteristics and oncologic outcomes of patients with stage I CRC and to identify risk factors for recurrence after curative surgery. However, we have some concerns regarding the exact data on rectal carcinoma recurrence after open and laparoscopic surgery, in reference to the location of cancer (lower/higher rectum) and the rate of recurrence according to the exact location on colon (rightand left-sided colon cancer). We feel that more precise data of recurrence after laparoscopic resection, especially in the case of rectum cancer, could be very useful. The authors showed that there is no difference in the rate of recurrence regarding the type of surgical approach, not considering colon and rectal cancer as separate categories, which might be interesting and somewhat useful. In the paper by Bonjer et al. [2], it is said that in the case in the lower rectal cancer, locoregional recurrence was more frequent in the group of patients treated by open surgery—12.7 versus 3.8% in the laparoscopy-surgery group. Bearing that in mind, we feel that recognition of separate categories of patients, in reference to the location of cancer, can provide more knowledge on the early treatment of CRC. Some recent cohort studies showed that right colon cancer is associated with poorer outcome compared to left sided colon cancer [3, 4], especially in the case of stage II or III of CRC. The authors of this paper have not carried out separate analysis on cancer recurrence regarding to the exact location of the cancer lesion. We feel that by creating separate groups of patients with rightand left-sided location of the cancer lesion, and their recurrence could bring more light on this topic, especially concerning stage I. Moritani in his study [5] demonstrated that patients with right-sided colon cancer had a significantly better 5-year disease-free survival than the patients with left-sided disease (100 vs. 95.2 %, P = 0.034) at stage I. According to this paper, right-sided colon cancer is a marginally significant risk factor for recurrence with advanced colon cancer (stage II and III), while on the contrary, right-sided colon cancer stage I has a significantly better prognosis and lower rate of recurrence. We hope that this additional data would give more accurate directives in treating patients with stage I colorectal cancer, in order to define the best approach and therapeutic strategy.

TNF α (-308G>A) And TNF-R1 (36A>G) Single nucleotide polymorphisms are strong risk factors for odontogenic keratocystic tumor development.

BACKGROUND Polymorphisms in genes encoding tumor necrosis factor-α (TNF-α) and its receptor TNF-R1 have been shown to affect one persons susceptibility to develop certain neoplastic diseases. The aim of the present association study was to investigate whether single nucleotide polymorphisms (SNPs) in TNF-α (-308G>A) and TNF-R1 (36A>G) genes modulate the susceptibility for keratocystic odontogenic tumors (KCOTs) development in Serbian patients. METHODS Genotyping was performed in 60 KCOT patients and 125 healthy individuals, using polymerase chain reaction/restriction fragment length polymorphism analysis. RESULTS A significant difference in genotype and allele frequencies was found between patients and controls for both SNPs (P < 0.05). Carriers of the TNF-α A variant had an eightfold increase of KCOT risk (OR = 8.12, 95% CI = 3.98-16.56, P < 0.0001), while carriers of the TNF-R1 G variant had approximately a fourfold increase of KCOT risk (OR=3.65, CI: 1.60-8.40, P = 0.001). CONCLUSIONS Our findings suggest that the two polymorphisms are strong risk factors for KCOT development in Serbian population.

Influence of Syrgical Trauma on Nitric Oxide and Nitrotyrosine Serum Levels in Patients Undergoing Laparoscopic or Conventional Cholecystectomy

Summary Background: Oxidative stress represents tissue damage caused by reactive forms of oxygen and nitrogen due to the inability of antioxidant mechanisms to reduce reactive forms into more stable ones. The aim of the study was to evaluate the influence of surgical trauma on nitric oxide (NO) and nitrotyrosine (NT) values in patients undergoing conventional and laparoscopic cholecystectomy. Methods: A prospective study included sixty patients from the Department of Emergency Surgery, Clinical Centre of Serbia who were operated for gallstone related chronic cholecystitis. All the patients enrolled in the study underwent cholecystectomy; the first group was operated conventionally (30 patients - control group), while the second group was operated laparoscopically (30 patients - treatment group). Results: There were no statistically significant differences in the values of NO and its postoperative changes in both groups, the conventionally operated group (p=0.943) and the laparoscopically operated group (p=0.393). We found an increase in NT values 24 hours postoperatively (p=0.000) in the conventionally operated patients, while in the group operated laparoscopically we didn’t find statistically significant changes in the values of NT (conventionally operated group (p=0.943) and laparoscopically operated group (p=0.393)). Conclusions: In our study, we found a significant increase in NT values 24 hours postoperatively in conventionally operated patients i.e. the control group, vs. the treatment group. Further randomized studies are needed for a better understanding of the impact of surgical trauma on oxidative stress response.

Serum Level of HMGB1 Protein and Inflammatory Markers in Patients with Secondary Peritonitis: Time Course and the Association with Clinical Status

Summary Background: Intra-abdominal infection in secondary peritonitis drives as excessive production of inflammatory mediators and the development of systemic inflammatory response syndrome (SIRS) or sepsis. Finding a specific marker to distinguish SIRS from sepsis would be of immense clinical importance for the therapeutic approach. It is assumed that high-mobility group box 1 protein (HMGB1) could be such a marker. In this study, we examined the time course changes in the blood levels of HMGB1, C-reactive protein (CRP), procalcitonin (PCT) and serum amyloid A (SAA) in patients with secondary peritonitis who developed SIRS or sepsis. Methods: In our study, we evaluated 100 patients with diffuse secondary peritonitis who developed SIRS or sepsis (SIRS and SEPSIS group) and 30 patients with inguinal hernia as a control group. Serum levels of HMGB1, CRP, PCT, and SAA were determined on admission in all the patients, and monitored daily in patients with peritonitis until discharge from hospital. Results: Preoperative HMGB1, CRP, PCT and SAA levels were statistically highly significantly increased in patients with peritonitis compared to patients with inguinal hernia, and significantly higher in patients with sepsis compared to those with SIRS. All four inflammatory markers changed significantly during the follow-up. It is interesting that the patterns of change of HMGB1 and SAA over time were distinctive for SIRS and SEPSIS groups. Conclusions: HMGB1 and SAA temporal patterns might be useful in distinguishing sepsis from noninfectious SIRS in secondary peritonitis.

Stenosis due to inflammatory bowel disease in patient with glycogenosis Ib-the rapeutical options

The occurrence of inflammatory bowel disease in patients with glycogen storage disease Ib is rare (GSDIb).We present the case of a young woman with the diagnosis of GSD-Ib Crohn-like colitis developed at age 27. She was under regular medical control because of severe malnutrition, secondary amenorrhea, leukopenia, neutropenia, hyperlipidaemia, dysfunctions of phagocytosis, and a subtotal stenosis of the ascending colon. Several months after diagnosing Crohn-like colitis, symptoms and signs of ileus developed, and she was admitted in the Emergency room department. Baloon dilatation with local corticosteroid injection was used for treatment. Clinical status of the patient markedly improved after this intervention. As far as we know, no similar cases with this kind of treatment are published.

First histological findings in rabbit model of peritoneal dialysis

Investigating peritoneal membrane alterations caused by peritoneal dialysis fluid during peritoneal dialysis in humans is still intriguing. That is why the study was aimed to provide rabbit peritoneal tissue samples suitable for histological analyses using a modified nonuremic infusion model of peritoneal dialysis on rabbit. A double-lumen central venous catheter, surgically placed in the peritoneal cavity of adult Chinchilla rabbit, was used for daily instillations of peritoneal dialysate. Peritoneal tissue samples were obtained during the catheter placement and removal and analyzed by light and transmission electron microscopy. The results of histological examinations showed that this modified non-uremic rabbit model of peritoneal dialysis is suitable for obtaining peritoneal tissue samples for light and transmission electron microscopy examination, and can be used to analyze the effects of different dialysis solutions on rabbit peritoneal membrane.