Effect of Intraperitoneal Chemotherapy with Regorafenib on IL-6 and TNF-α Levels and Peritoneal Cytology: Experimental Study in Rats with Colorectal Peritoneal Carcinomatosis.

Cytoreductive surgery (CRS), combined with hyperthermic intraperitoneal chemotherapy, has significantly improved survival outcomes in patients with peritoneal carcinomatosis from colorectal cancer (CRC). Regorafenib is an oral agent administered in patients with refractory metastatic CRC. Our aim was to investigate the outcomes of intraperitoneal administration of regorafenib for intraperitoneal chemotherapy (IPEC) or/and CRS in a rat model of colorectal peritoneal metastases regarding immunology and peritoneal cytology. A total of 24 rats were included. Twenty-eight days after carcinogenesis induction, rats were randomized into following groups: group A: control group; group B: CRS only; group C: IPEC only; and group D: CRS + IPEC. On day 56 after carcinogenesis, euthanasia and laparotomy were performed. Serum levels of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) as well as peritoneal cytology were investigated. Groups B and D had statistically significant lower mean levels of IL-6 and TNF-α compared to groups A and C, but there was no significant difference between them. Both B and D groups presented a statistically significant difference regarding the rate of negative peritoneal cytology, when compared to the control group, but not to group C. In conclusion, regorafenib-based IPEC, combined with CRS, may constitute a promising tool against peritoneal carcinomatosis by altering the tumor microenvironment.

Two case reports of mesenteric and retroperitoneal actinomycosis and a narrative review of the relevant literature.

Introduction: Actinomycosis is an uncommon subacute or chronic suppurative bacterial granulomatous infectious disease with clinical heterogeneity. The majority of actinomycosis cases were of extra-abdominal origin, with oro-cervico-facial cases representing 55%, abdominopelvic representing 20%, and thoracic representing 15% of total reports. Currently, abdominal actinomycosis incidence is approximately 1 case per 119,000 people, being found three times more frequently among males. We report two rare clinical presentations of abdominal actinomycosis affecting the mesentery and the retroperitoneum, respectively. Case Report 1: A 58-year-old Caucasian male presented to our clinic with abdominal pain in the right upper quadrant. Pre-operative evaluation, although inconclusive, showed a mesocolic mass infiltrating the right and transverse colon. The patient underwent exploratory laparotomy. After partial resection of the mass, the histopathology report demonstrated mesenteric actinomycosis. Case Report 2: A 40-year-old Caucasian male presented to our clinic complaining about a mucopurulent material from an orifice at the right inguinal region. After appropriate work-up, a large abdominopelvic, stellate mass (75 x 22.8 mm) in the retroperitoneum was revealed. Surgery along with the appropriate antibiotics was used to treat the patient. Conclusion: Preoperative suspicion and diagnosis of actinomycosis are very challenging, with a high rate of misdiagnosis often resulting in delayed treatment. Our case reports highlight that abdominal actinomycosis should always be part of differential diagnosis, especially when there is involvement of multiple organs. The gold standard treatment of actinomycosis is surgical excision with prolonged antibiotic treatment.

The Role of Adipose Tissue Mesenchymal Stem Cells in Colonic Anastomosis Healing in Inflammatory Bowel Disease: Experimental Study in Rats.

(1) Background: A surgical operation on an inflamed bowel is, diachronically, a challenge for the surgeon, especially for patients with inflammatory bowel disease. Adipose tissue-derived mesenchymal stromal cells are already in use in clinical settings for their anti-inflammatory properties. The rationale of the current study was to use AdMSCs in high-risk anastomoses to monitor if they attenuate inflammation and prevent anastomotic leak. (2) Methods: a total of 4 groups of rats were subjected to a surgical transection of the large intestine and primary anastomosis. In two groups, DSS 5% was administered for 7 days prior to the procedure, to induce acute intestinal inflammation. After the anastomosis, 5 × 106 autologous AdMSCs or an acellular solution was injected locally. Macroscopic evaluation, bursting pressure, hydroxyproline, and inflammatory cytokine expression were the parameters measured on the 8th post-operative day. (3) Results: Significantly less intra-abdominal complications, higher bursting pressures, and a decrease in pro-inflammatory markers were found in the groups that received AdMSCs. No difference in VEGF expression was observed on the 8th post-operative day. (4) Conclusions: AdMSCs attenuate inflammation in cases of acutely inflamed anastomosis.

Laparoscopic para-aortic lymphadenectomy for metastatic colon cancer in a patient with left-sided inferior vena cava: a case report.

Transposition of inferior vena cava, or, left-sided inferior vena cava (LS-IVC) is a rare clinical entity, in which the inferior vena cava ascends along the left side of the abdominal aorta. Literature contains mainly clinical case reports. Although it is usually not associated with clinical symptomatology, this anomaly should be detected during preoperative planning to avoid iatrogenic injuries intraoperatively. We present a case of left-sided inferior vena cava encountered during laparoscopic lymphadenectomy in a 45-year-old man with previous laparoscopic hemicolectomy due to colon adenocarcinoma. Preoperative CT abdomen revealed the left-sided location of infrarenal IVC and laparoscopic trans-peritoneal aortic lymphadenectomy was decided. Intraoperatively, transposition of inferior vena cava was confirmed in accordance with the CT findings. Resection of lymph node block was conducted with no complications and with minimal blood loss. The postoperative course was uneventful, and the patient was discharged from the hospital the day following surgery. In conclusion, transposition of the inferior vena cava, although rare, constitutes an anatomical variant that should be identified preoperatively to decrease intraoperative risks. Several anatomical variants have been associated with left-sided inferior vena cava.

The feasibility and effect of intraperitoneal administration of regorafenib on peritoneal carcinomatosis from colorectal cancer in the rat.

AIM: Our goal was to investigate the potential use and efficacy of regorafenib for IPEC in an animal model of colorectal derived peritoneal metastases. Twenty four male rats were included. Carcinogenesis was induced in all rats through intraperitoneal injection of cancer. MATERIAL AND METHODS: Cells at T0. At T1(Day 28) they were randomly allocated 1:1:1:1 into 4 groups and underwent median laparotomy and the corresponding intervention. Specifically, Group A: no other intervention; Group B: cytoreductive surgery; Group C: intraperitoneal chemotherapy with regorafenib; and Group D: cytoreductive surgery and intraperitoneal chemotherapy with regorafenib. At T2 (Day 56) rats were euthanized and laparotomy was performed for further investigation. The primary outcome was the experimental Peritoneal Cancer Index (ePCI) at T2. Secondary outcomes include relative change of body weight between T1 and T2, weight of the ascites, anastomotic leak/peritonitis and death. RESULTS: The ePCI was significantly lower in Group D as opposed to all other groups. Comparing Group C versus Group A we found a trend towards lesser tumor progression, but no significant difference. Growth of rats in Group D was significantly least affected compared to all other groups. Animals undergoing CRS in Group B developed less ascites than Group A and C. Less ascites was found in Group D compared to Group A and C. CONCLUSIONS: Intraperitoneal chemotherapy with regorafenib combined with cytoreductive surgery may impair metastases' progression. KEY WORDS: Regorafenib, Chemotherapy, Cytoreductive surgery, Colorectal cancer, Intraperitoneal injection.

Effect of N-acetyl-L-cysteine on inflammation after intraperitoneal mesh placement in a potentially contaminated environment: An experimental study in the rat.

BACKGROUND: The use of prosthetic meshes in abdominal wall reconstruction is a well-established approach; however, in certain cases where a bowel resection coexists its application is disputed. Any underlying inflammatory process may augment adhesion formation which is a major postoperative complication. In this animal study, our aim was to investigate the effect of N-acetyl-l-cysteine (NAC) on adhesion formation and the expression of inflammatory markers when a mesh was used in a clean or a potentially contaminated environment. METHODS: Sixty male Wistar rats were randomly and equally allocated in 3 groups: A, B and C. Animals in all groups underwent laparotomy, a prosthetic mesh was placed and chemoprophylaxis with ciprofloxacin was administered. In groups B and C an enterectomy was also performed. NAC was injected intraperitoneally in group C. Adhesion formation, IL-1a, IL-6, TNF-a and histological data including fibrosis, neutrophils' infiltration and neovascularization were assessed. Mesh samples were sent for cultivation. RESULTS: Adhesion formation was significantly less and inflammation markers were also lower in group C compared to group B (p<0.05). Histological findings were significant for greater fibrosis, neutrophils' infiltration and neovascularization in group B compared to both group A and C. Regarding mesh cultures, more specimens were tested positive in group B (p <0.05). Outcomes between group A and C did not differ. CONCLUSION: NAC effectively ameliorated adhesion formation and inflammation in a potentially septic environment where a prosthetic mesh was placed.

Transdiaphragmatic Intercostal Hernia-An Unusual Hepatic Injury After a Car Accident: A Case Report and Review of the Literature.

Transdiaphragmatic intercostal hernia, in which the abdominal contents of the hernia protrude through the diaphragm and the thoracic wall defect. is a very rare type of hernia with only a few cases having been reported in the literature. That type of hernia is usually manifested in male patients after trauma, penetrating or blunt. It is frequently presented with a palpable thoracic mass and pain. The indicated treatment is surgery. We present the case of a 60-year-old female admitted to the hospital after a car accident and suffered multiple rib fractures (6th, 7th, 8th right ribs / 7th, 8th, 9th left ribs), as well as flail thorax, hemothorax bilaterally, left subcutaneous emphysema and swelling of soft tissues of the right lateral thoracoabdominal wall. CT scan revealed herniation of hepatic parenchyma and intestinal loops into the thorax. The patient was treated surgically, and his postoperative course was uneventful. We also review the relevant literature concerning this transdiaphragmatic, intercostal hernia and identify 42 cases. Transdiaphragmatic intercostal hernia is a rare condition, usually manifested in male patients after trauma, penetrating or blunt. It is frequently presented with a palpable thoracic mass and pain. The indicated treatment is surgery.

Giant Adrenocortical Carcinoma: A Case Report and Review of the Relevant Literature.

BACKGROUND Adrenocortical carcinomas are rare and aggressive tumors often diagnosed as incidentalomas. The malignancy can present with abnormal hormone secretion or the tumor may be non-functioning and present as a palpable mass causing discomfort. Here, we present a case of an adrenal cortical carcinoma originally identified as an incidentaloma. CASE REPORT A 63-year-old woman presented with abdominal pain and discomfort. A large abdominal mass, occupying the left upper and lower quadrant, was palpated. Imaging revealed a mass occupying the left abdomen between the stomach and the spleen, applying pressure on the pylorus, duodenum, splenic vessels, and pancreas. The mass size was 21.2×13×14.6 cm. Hormonal investigations were normal. Surgical exploration was performed, and the tumor was excised. Pathological analysis revealed an adrenocortical carcinoma and the patient underwent adjuvant chemotherapy. Twelve months later, the carcinoma recurred. The patient underwent a second operation in which the recurrent mass was excised along with the tail of the pancreas and a small part of the left lobe of the liver. The postoperative period was uneventful, and the patient was discharged home on the 7th postoperative day. No further adjuvant therapy was applied. The patient remains disease-free 18 months after the reoperation. CONCLUSIONS Giant adrenocortical carcinomas, although rare, pose a challenge to the surgical team both diagnostically and therapeutically. Surgical excision with the appropriate oncologic support can guarantee excellent outcomes.

Case Report: A Virilizing Adrenal Oncocytoma.

A 64-year-old female was admitted to our clinic with a 9-cm-sized adrenal mass. The patient's main symptom was hirsutism, which included thinning scalp hair and excessive hair growth over her torso and arms. Upon investigation, elevated values of testosterone, androsterone D4, and DHEA-S were found. Contrast-enhanced abdominal CT and MRI scans revealed a heterogenous large mass (diameter 9 × 8.5 cm) with focal calcifications, necrotic areas, and a clear distinction from the adjacent structures. The patient underwent a right adrenalectomy. The histological examination of the tumor revealed a borderline adrenocortical oncocytoma. The patient had an uncomplicated postoperative course and was discharged on postoperative day 8. Similar cases reported in the literature are also being reviewed in this case report.

Changes of Gastric Secretion after Bolus and Slow Intravenous Administration of Bombesin and Neurotensin.

Objectives:The aim of the present study was to evaluate the changes caused by intravenous administration of regulatory peptides, bombesin (BBS) and neurotensin (NT), on gastric secretion, serum gastrin, and plasma levels of bombesin-1ike immunoreactivity (BLI) and neurotensin. Materials and methods: Fourteen dogs underwent an upper gastrointestinal tract operation and a Pavlov pouch for the concentration of gastric fluids was formed. The experimental animals were divided into two groups. Peptides were given one month after the second operation and after fasting for 12 hours. In group A, the effects of BBS were studied after a rapid 1 ìg/kg body weight dose and a slow 30´ 0.5 ìg/kg body weight dose administration intravenously. Correspondingly to group B the effects of NT were studied in the same way. Results:The rapid intravenous infusion of BBS caused a very significant increase in gastrin levels, BLI in plasma, volume and HCl of the gastric fluids. The same results, plus a significant decrease in gastric pH, were observed following slow intravenous infusion of BBS. Concerning the NT, rapid administration caused a significant decrease in the volume of gastric fluids. Slow NT administration of caused a significant reduction in gastric fluid volume and in HCl. On the contrary, pH was significantly increased. Conclusion:Bombesin increases plasma gastrin levels and HCl secretion. Neurotensin administration causes a decrease in HCl secretion without affecting gastrin levels in plasma.