Dual activity of Minnelide chemosensitize basal/triple negative breast cancer stem cells and reprograms immunosuppressive tumor microenvironment.

Triple negative breast cancer (TNBC) subtype is characterized with higher EMT/stemness properties and immune suppressive tumor microenvironment (TME). Women with advanced TNBC exhibit aggressive disease and have limited treatment options. Although immune suppressive TME is implicated in driving aggressive properties of basal/TNBC subtype and therapy resistance, effectively targeting it remains a challenge. Minnelide, a prodrug of triptolide currently being tested in clinical trials, has shown anti-tumorigenic activity in multiple malignancies via targeting super enhancers, Myc and anti-apoptotic pathways such as HSP70. Distinct super-enhancer landscape drives cancer stem cells (CSC) in TNBC subtype while inducing immune suppressive TME. We show that Minnelide selectively targets CSCs in human and murine TNBC cell lines compared to cell lines of luminal subtype by targeting Myc and HSP70. Minnelide in combination with cyclophosphamide significantly reduces the tumor growth and eliminates metastasis by reprogramming the tumor microenvironment and enhancing cytotoxic T cell infiltration in 4T1 tumor-bearing mice. Resection of residual tumors following the combination treatment leads to complete eradication of disseminated tumor cells as all mice are free of local and distant recurrences. All control mice showed recurrences within 3 weeks of post-resection while single Minnelide treatment delayed recurrence and one mouse was free of tumor. We provide evidence that Minnelide targets tumor intrinsic pathways and reprograms the immune suppressive microenvironment. Our studies also suggest that Minnelide in combination with cyclophosphamide may lead to durable responses in patients with basal/TNBC subtype warranting its clinical investigation.

The Relationship Between Small Peritoneal Flap Defects and Postoperative Seroma in TAPP Repair of Inguinal Hernias.

OBJECTIVE: Total abdominal preperitoneal (TAPP) is one of the most frequently used surgical treatment methods in the treatment of inguinal hernia (IH). One of the most common early postoperative complications after hernia repair is seroma/hematoma. In this study, we aimed to study the role of unclosed peritoneal flap defects on the development of postoperative seroma. MATERIAL AND METHODS: The study was performed retrospectively in 2 university hospitals. All patients over the age of 18 years who underwent laparoscopic TAPP surgery in Istanbul Yeni Yüzyil University Gaziosmanpasa Hospital General Surgery Clinic and Van Yüzüncü Yil University Faculty of Medicine General Surgery Clinic between January 1, 2018, and December 31, 2021, were included. Patients were divided into those with peritoneal defects (group 1) and those without (group 2). Whether there was a peritoneal defect or not was compiled from video recordings. In addition, risk factors affecting the development of seroma were determined. RESULTS: A total of 250 patients, 16 (6.4%) women and 234 (93.6%) men, were included in the study. There were bilateral hernias in 35 (14%) patients, and a total of 320 hernias were analyzed in the study. It was determined that an American Society of Anaesthesiologists (ASA) III score increased the risk of seroma 15.97 fold (P<0.001, 95% CI, 4.94 to 51.56), direct hernia type increased risk 7.1 fold (P<0.03, 95% CI, 1.204 to 42.422), hernia descending into scrotum increased risk 22.48 fold (P<0.001, 95% CI, 6.66 to 75.84) and closure of the peritoneal flap completely without leaving any defect increased the risk of seroma 8.67 fold (P<0.001, 95% CI, 3.254 to 23.115). CONCLUSIONS: The presence or leaving of small-diameter defects on the peritoneal flap may reduce seroma development without increasing the risk of complications. Prospective randomized studies are required to reach definitive conclusions.

Risk of Conversion from Laparoscopic Appendectomy to Open Surgery: The Role of Clinical and Radiological Factors in Prediction.

Introduction: Laparoscopic appendectomy is the most preferred surgical method in the treatment of acute appendicitis. In our study, we aim to determine the clinical and radiological factors affecting conversion from laparoscopic appendectomy to open surgery. Materials and Methods: All patients older than 18 years, who were operated on with the diagnosis of acute appendicitis in the General Surgery clinic of Prof. Dr. Ilhan Varank Training and Research hospital between January 2020 and January 2022, were included in the study. The data consisting of clinical, laboratory, and radiological (computed tomography) findings of the patients were evaluated retrospectively. The patients were divided into two groups as those whose surgery was completed laparoscopically (Group 1) and those converted from laparoscopic appendectomy to open surgery (Group 2). The risk of conversion to open surgery was analyzed by binary logistic regression analysis as univariate and multivariate models. Results: Appendectomy was performed in 831 patients within the specified period. The surgery of 31 (3.73%) patients started laparoscopically; however, they were completed by converting to open surgery. Multivariable analysis showed that the risk of conversion to open surgery increased with leukocyte count, Alvarado score and with the presence of periappendiceal fluid and lymphadenopathy on CT. Conclusion: Our study shows that patients with high risk of returning to open surgery can be identified preoperatively with the risk analysis method in which clinical, laboratory, and radiological findings are evaluated together. We conclude that, starting the operation of these patients with the open technique from the beginning will prevent unnecessary expenditures and reduce morbidities.

Asymptomatic synthetic vascular graft migration to duodenum after living donor liver transplantation: report of two cases.

BACKGROUND: In this study, we present the results of two patients with vascular graft migration to the duodenum after liver transplantation. METHODS: The results of two patients who underwent living donor liver transplantation and vascular graft to the duodenum were evaluated. RESULTS: In our center, 201 liver transplants were performed, including 154 a right lobe living donor liver transplant. A synthetic graft was used to reconstruct segment 5 and 8 hepatic veins in 78 of the 154 LDLT. During the mean follow-up 19.6 ± 12.1 months (1-44 months), graft migrated to the duodenum in two patients who were present in this study. Contrary to the literature, it was followed nonoperatively. No problem was observed in the follow-up process. CONCLUSION: In patients with vascular graft migration to the duodenum after living liver transplantation, non-operative follow-up can be performed in appropriate patients.

Comparison of thyroid surgery experiences of "East" and "West" regions in Turkiye.

OBJECTIVE: This study aimed to evaluate the differences between the types of thyroidectomy surgeries and surgical treatment approaches according to thyroid pathology results, in Turkiye's two non-endemic regions. METHODS: Two different centers of the country, which differ in many respects and are non-endemic for thyroidal diseases were included in the study. Data on patients from both sexes, who underwent thyroidectomy in the western (1st center) and the eastern (2nd center) regions between 2011 and 2017 have been reviewed. RESULTS: Two hundred and forty patients from Istanbul (1st center) and 992 patients from Van (2nd center); a total of 1232 patients were included in the study. According to the pre-operative ultrasonography and laboratory results, toxic nodular goiter and multinodular goiter were the most common diseases in the first and second centers, respectively. There was a significant statistical difference between the radiological diagnostic findings between the two centers (p<0.001). The rate of bilateral total thyroidectomy in the first center was 82.5% (198 patients), whereas this rate was 58.5% (555 patients) in the second center. The type of surgery may change from center to center, (p<0.001). The most common early post-thyroidectomy complication was hypocalcemia in both centers. CONCLUSION: The results from only two centers from the western and eastern Turkiye show that there is a difference between the thyroidectomy preferences. Future similar national studies will contribute to the provision of a consensus in surgical treatment of thyroid diseases.

Factors Affecting Bile Complications After Liver Transplantation: Single-Center Experience.

Objectives: In this study, we aimed to investigate the surgical technique and biochemical parameters that affect biliary complications in liver transplants from live and cadaver in our center. Methods: In this study, 141 patients who underwent liver transplants at Istanbul Yeni Yüzyil Universty Gaziosmanpasa Hospital organ transplant center between January 2018 and January 2020 were included in the study. The patients were monitored for 12-24 months. The patients included in the present study were examined retrospectively. Factors that may cause biliary tract complications and treatment modalities for complications were examined. Results: In this study, liver transplantation from 124 living donors and 17 cadavers was performed. Twenty-three patients were under the age of 18. Only seven of 39 biliary complications were operated on. The rate of finding the right graft in patients with biliary complications was higher (p<0.05). There was no statistically significant difference between the groups concerning left, left lateral, and whole graft presence (p=0.561, p=0.172, and p=0.057, respectively). Double biliary anastomosis was to be higher in the biliary complication group, but there was no statistically significant difference (p=0.086). Conclusion: Biliary complications are common, especially in liver transplants taken from the right lobe. Significant patient survival can be achieved with an early diagnosis and an appropriate treatment approach.

Urological injuries in the civil war of Libya.

BACKGROUND: In this article, we aimed to evaluate results of patients who acquired various injuries during Libya civil war who then were transferred to our facility with genitourinary trauma for further assessment and treatment. METHODS: A total of 121 wounded patients, including 21 (17.3%) with 1 or more combined urogenital injuries, were treated at Yeni Yüzyil University Private Gaziosmanpasa Hospital from October 2014 to September 2016. RESULTS: Of the 21 patients, 13 (61.9%) were injured by explosive weapons, while the rest 8 (38.1%) had bullet wounds. The 21 urogenital injuries were to the kidney in 7 cases (33.4%), ureter in 5 (23.8%), bladder in 5 (23.8%), scrotum in 2 (9.5%), and penis in 2 (9.5%). There was associated damage to organs other than the urogenital system in 21 patients (100%). Two patients had nephrectomies performed on-site medical facility. The rest of patients had no urogenital organ resections. Urogenital trauma had higher rates of liver damage, generalized infection, blood transfusions, and longer hospital stay. CONCLUSION: Knowing that war related surgery patients should be approached as a distinct and non-standard category, every case must be evaluated individually. Patients should be evaluated in a multidisciplinary approach and physicians should be aware of infections affecting morbidity and mortality.

Is the incision type important for the development of hernia in liver transplant patients?

OBJECTIVE: In this study, we aimed to investigate the rates and causes of incisional hernia that developed in the postoperative follow-up of patients who underwent liver transplantation. MATERIAL AND METHOD: The results of patients who underwent LT by using three different incisions at the Istanbul Yeni Yüzyil University Gaziosmanpasa Hospital organ transplant center between January 2015 and December 2019 were retrospectively analyzed. Patients were divided into Chevron (group-1), reverse T (group-2), and J incisions (group-3) and hernia development rates were examined. RESULTS: There was no significant difference in terms of incisional hernia in groups 1 and 2 according to the incision type (p = .723). Incisional hernia rate was significantly lower in the J incision group (p < .001). When the factors that increase the development of hernia in all LT patients were examined, it was seen that male gender (p = .021), high BMI rate (p = .003), postoperative bleeding (p = .018), and wound infection (p = .039) caused a significant increase in risk. CONCLUSION: The incision, which is made during liver transplant, is important for the development of hernia. The J incision has a low hernia development rate without causing access problems. Regardless of the incision, high BMI index, male gender, postoperative bleeding, and wound infection increase the development of incisional hernia in liver transplant patients.

When Should I Use an Additional Port at the Time of Three-Port Laparoscopic Cholecystectomy?

Objective: Today, it is recommended that the laparoscopic cholecystectomy (LC) is made with standard three ports. In this study, we aimed to determine the preoperative and intraoperative factors that require the use of an additional fourth port during three-port LC. Materials and Methods: All patients who started LC with three ports between January 1, 2018 and December 31, 2019 were included in the study. The patients were divided into two groups as those who underwent three-port LC and those who required additional ports. Independent parameters affecting the transition from three ports to four ports were analyzed using logistic regression analysis. The patients who underwent LC with three ports were included in Group 1 and the patients requiring an additional port were included in Group 2. Results: A total of 234 patients (139 women and 95 men) were included in the study. The average age of patients was 52.95 ± 16.26 (20-89) and body mass index is 28.64 ± 5.4 (15.73-48.89), respectively. Three ports were used in 148 patients (Group 1), and an additional fourth port was used in 42 patients (Group 2). Female gender, history of upper laparotomy, presence of acute infection findings, urgent surgery, and advanced age were observed to increase the use of additional ports. In multivariate analysis, it was shown that the presence of hepatic barrier (P < .001) and the presence of complete adhesion in the gallbladder (P < .001) significantly increased the use of additional trocars during LC. In addition, female gender was found to cause an increase of 6.62 times (P < .001). Conclusion: Many factors may require the use of additional ports during three-port LC. The use of an additional fourth port should not be avoided, especially in cases where hilum dissection is prevented due to liver origin, in female patients and in cases with complete adhesion to the gallbladder.

Surgical approach to recurrent secondary aortoenteric fistulas: A case report.

The increasing number of abdominal aortic grafts due to abdominal aortic aneurysms has caused secondary aortoenteric fistulas to be seen more frequently as a cause of gastrointestinal bleeding. High index of suspicion plays a significant role in the diagnosis in patients having clinical symptoms ranging from fecal occult blood to massive gastrointestinal bleeding, accompanied by hemorrhagic shock. A 65-year-old male patient developed two secondary aortoenteric fistulas consecutively. The first one was aortic graft-jejunal and the second one was aortic graft-duodenal in a short period. Secondary aortoenteric fistula developed after aortobifemoral bypass. The patient underwent graft revision and jejunal repair. He was reoperated three months later due to the newly developed aortic graft-duodenal fistula. The duodenal defect was closed, and an extra-anatomic aortoiliac bypass was performed to avoid graft-related enteric fistula. The patient was discharged uneventfully and was free from any complication at nine months after surgery.

The Role of Dual-Energy Computed Tomography in Locating Gastrointestinal Tract Perforations.

Objective With each passing day, dual-energy computed tomography (DECT) is being used more frequently in the evaluation of abdominal pathologies. In this article, we aimed to assess the role of dual-energy CT in locating gastrointestinal perforations, which are among the causes of acute abdomen. Materials and methods All patients who underwent DECT due to acute abdomen in a COVID-19 designated hospital between June 1st, 2020 and December 31st, 2020, who were found to have gastrointestinal tract (GIT) perforation and underwent surgery were included in the study. DECT results and intraoperative findings of the patients were compared. Results Thirteen patients (nine males and four females) who underwent DECT for acute abdomen and were diagnosed with perforation in the gastrointestinal system were included in the study. The mean age of the patients was 57.6 years (range: 11-85 years). Two patients had gastric perforation, three had duodenal perforations, and one patient had a perforation in the gallbladder wall. Two patients were diagnosed with jejunal perforations, one patient with Meckel's diverticulum, and three patients with colorectal perforation. Although free air was detected in the abdomen of one patient, perforation could not be located. In patients with GIT perforation who were operated on following DECT imaging, the perforation location shown on DECT correlated 100% with the perforation locations detected during surgery. Conclusion DECT is significantly effective in planning surgical treatment and determining the foci of perforation in GIT perforations.

Surgical treatment of liver hydatid cyst before autologous stem cell transplantation; presentation of two cases with literature review.

Hydatid cyst, caused by Echinococcus granulosus, is a parasitic disease which is frequently seen in endemic areas. The disease can be seen as an isolated entity or simultaneously with other diseases. Treatment of hydatid cyst in patients with malignancy as well as in patients in need of transplantation is still unclear. Although there is information in the form of case reports, a large number of patient data are needed to create a consensus on the management of these patients. We reviewed two cases with the need of autologuous stem cell transplantation which underwent liver hydatic cystectomy before transplantation.

A Rare Case of Pancreatic Tail Hydatid Cyst with Incidental Adenocarcinoma of the Pancreatic Body.

Pancreatic hydatid cyst is a rare disease found mostly in endemic regions. Having no specific clinical signs, it may present with tension related abdominal pain, dyspepsia, a palpable mass, and signs of external pressure on the surrounding organs in accordance with localization of the lesion. Pancreatic carcinoma as a neoplastic pathology with poor prognosis can have various clinical presentations changing with localization of the tumor which sometimes has cystic components. Due to the distinct nature of these pathologies, surgical approach can be fairly different. In this report, we present a case of a 70-year-old patient who had an isolated hydatid cyst in the tail of the pancreas with an incidental pancreatic carcinoma in the corpus of the pancreas. The patient was treated with a subtotal pancreatectomy, having no problems in the postoperative period leading to uncomplicated discharge.

Embracing the Future of Surgery: Gastric Cancer Resection Within One Month of Left Ventricular Assist Device Implantation.

Left ventricular assist devices (LVADs) have been implanted recently, with increasing frequency, to treat advanced heart failure with good survival rates. Since heart failure is most prevalent in patients above 70 years of age, LVAD implantations are increasing particularly in this cohort. On the other hand, due to a higher incidence of malignant tumors in the elderly population, there is a significant cohort of patients having concurrent indications for LVAD implantation. Herein, we report a case of complicated gastric malignancy that was encountered soon after the implantation of an emergent LVAD with ensuing treatment difficulties and ethical considerations. Keeping in mind the fairly high life expectancy for both groups, there is a predisposition to the notion that simultaneous procedures can and should be applicable to a selected group of patients with end-stage heart failure.

Parasitic Appendicitis: A Novel Laparoscopic Approach for the Prevention of Peritoneal Contamination.

BACKGROUND/AIM: Although rare, parasitic infection can cause acute appendicitis and result in contamination of the peritonea during appendectomy. The goal of this study was to summarize our experiences with parasitic appendicitis and describe a novel laparoscopic technique to prevent contamination. METHOD: All patients diagnosed with acute appendicitis who underwent appendectomy between January 2016 and January 2017 were included in the study. All appendectomies were performed using the standard three-port laparoscopic method, and a video recording was made of each procedure. Following separation of the mesoappendix, a single endoloop was placed in the base of the appendix, and the appendix was then transected 3-4 mm above the clamp with the aid of a thermal cauterizing/sealing device. The appendix was extracted from the 10 mm trocar hole below the umbilicus and placed inside a bag prepared from a glove. After pathological confirmation of parasitic appendicitis, medical records were retrospectively analyzed in each case for whether peritoneal contamination had occurred or not. RESULTS: Out of 97 appendectomies, parasitic infection was observed in 4 cases, as confirmed by pathological examination. In two of these patients, E. vermicularis was detected, while the other two were infected with Balantidium coli. Intraoperative contamination did not occur in any of the cases, and retrospective review of the video recordings indicated no peritoneal contamination. CONCLUSION: As a result of the coagulation and sealing effects of thermal devices, airtight seals were created on the residual appendiceal stumps, and consequently, no contamination was observed in any of the cases.