Current considerations on intraductal papillary neoplasms of the bile duct and pancreatic duct.

Pancreatobiliary intraductal papillary neoplasms (IPNs) represent precursors of pancreatic cancer or bile duct cholangiocarcinoma that can be detected and treated. Despite advances in diagnostic methods, identifying these premalignant lesions is still challenging for treatment providers. Modern imaging, biomarkers and molecular tests for genomic alterations can be used for diagnosis and follow-up. Surgical intervention in combination with new chemotherapeutic agents is considered the optimal treatment for malignant cases. The balance between the risk of malignancy and any risk of resection guides management policy; therefore, treatment should be individualized based on a meticulous preoperative assessment of high-risk stigmata. IPN of the bile duct is more aggressive; thus, early diagnosis and surgery are crucial. The conservative management of low-risk pancreatic branch-duct lesions is safe and effective.

Management of obstructed colorectal carcinoma in an emergency setting: An update.

Colorectal carcinoma is common, particularly on the left side. In 20% of patients, obstruction and ileus may be the first clinical manifestations of a carcinoma that has advanced (stage II, III or even IV). Diagnosis is based on clinical presentation, plain abdominal radiogram, computed tomography (CT), CT colonography and positron emission tomography/CT. The best management strategy in terms of short-term operative or interventional and long-term oncological outcomes remains unknown. For the most common left-sided obstruction, the first choice should be either emergency surgery or endoscopic decompression by self-expendable metal stents or tubes. The operative plan should be either one-stage or two-stage resection. One-stage resection with on-table bowel decompression and irrigation can be accompanied or not accompanied by proximal defunctioning stoma (colostomy or ileostomy). Primary anastomosis is more convenient but has increased risks of anastomotic leakage and morbidity. Two-stage resection (Hartmann's procedure) is safer and the most widely used despite temporally affecting quality of life. Damage control surgery in high-risk frail patients is less frequently performed since it can be successfully substituted with endoscopic stenting or tubing. For the less common right-sided obstruction, one-stage surgical resection is more beneficial than endoscopic decompression. The role of minimally invasive surgery (laparoscopic or robotic) is a subject of debate. Emergency laparoscopic-assisted management is advantageous to some extent but requires much expertise due to inherent difficulties in dissecting the distended colon and the risk of rupture and subsequent septic complications. The decompressing stent as a bridge to elective surgery more substantially decreases the risks of morbidity and mortality than emergency surgery for decompression and has equivalent medium-term overall survival and disease-free survival rates. Its combination with neoadjuvant chemotherapy or radiation may have a positive effect on long-term oncological outcomes. Management plans are crucial and must be individualized to better fit each case.

The Effectiveness of Adipose Tissue-Derived Mesenchymal Stem Cells Mixed with Platelet-Rich Plasma in the Healing of Inflammatory Bowel Anastomoses: A Pre-Clinical Study in Rats.

Introduction: Multiple factors have been linked with increased risk of anastomotic leak in bowel surgery, including infections, inflammatory bowel disease, patient comorbidities and poor surgical technique. The aim of this study was to investigate the positive effect, if any, of adipose derived mesenchymal stem cells (MSCs) mixed with platelet-rich plasma (PRP) in the healing of bowel anastomoses, in an inflammatory environment after establishment of experimental colitis. Materials and Methods: Thirty-five male Wistar rats were divided into five groups of seven animals: normal controls, colitis controls, PRP, MSCs, and PRP+MSCs. All groups underwent laparotomy, one-cm segmental colectomy and anastomosis in situ. In the colitis group, colectomy was performed at the affected area. Colitis was previously established by transrectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) except for the normal controls. Post-mortem histopathological, tissue hydroxyproline and anastomotic bursting pressure (ABP) assessments were performed. The Mann-Whitney U test was used to assess statistical significance differences between groups. Results: No perioperative mortality was noted. Tissue hydroxyproline and ABP were significantly increased in the group of PRP+MSCs compared to colitis controls (p = 0.0151 and p = 0.0104, respectively). Inflammatory cell infiltration was lower and fibroblast activity higher in PRP+MSCs group, but not statistically significant (p > 0.05). Neoangiogenesis (p = 0.0073) and anastomotic area epithelialization (p = 0.0182) were significantly higher in PRP + MSCs group compared to colitis controls. Discussion: The synergistic effect of the PRP and MSCs is apparently responsible for the improved healing markers in bowel anastomoses even on inflammatory bowel. This gives hope for primary anastomoses and stoma saving in many emergency and/or elective circumstances, especially in immunocompromised or malnourished patients, even in cases with inflammation or peritonitis. Clinical studies should follow in order to support the clinical application of PRP+MSCs in gastrointestinal anastomoses.

New trends in diagnosis and management of gallbladder carcinoma.

Gallbladder (GB) carcinoma, although relatively rare, is the most common biliary tree cholangiocarcinoma with aggressiveness and poor prognosis. It is closely associated with cholelithiasis and long-standing large (> 3 cm) gallstones in up to 90% of cases. The other main predisposing factors for GB carcinoma include molecular factors such as mutated genes, GB wall calcification (porcelain) or mainly mucosal microcalcifications, and GB polyps ≥ 1 cm in size. Diagnosis is made by ultrasound, computed tomography (CT), and, more precisely, magnetic resonance imaging (MRI). Preoperative staging is of great importance in decision-making regarding therapeutic management. Preoperative staging is based on MRI findings, the leading technique for liver metastasis imaging, enhanced three-phase CT angiography, or magnetic resonance angiography for major vessel assessment. It is also necessary to use positron emission tomography (PET)-CT or 18F-FDG PET-MRI to more accurately detect metastases and any other occult deposits with active metabolic uptake. Staging laparoscopy may detect dissemination not otherwise found in 20%-28.6% of cases. Multimodality treatment is needed, including surgical resection, targeted therapy by biological agents according to molecular testing gene mapping, chemotherapy, radiation therapy, and immunotherapy. It is of great importance to understand the updated guidelines and current treatment options. The extent of surgical intervention depends on the disease stage, ranging from simple cholecystectomy (T1a) to extended resections and including extended cholecystectomy (T1b), with wide lymph node resection in every case or IV-V segmentectomy (T2), hepatic trisegmentectomy or major hepatectomy accompanied by hepaticojejunostomy Roux-Y, and adjacent organ resection if necessary (T3). Laparoscopic or robotic surgery shows fewer postoperative complications and equivalent oncological outcomes when compared to open surgery, but much attention must be paid to avoiding injuries. In addition to surgery, novel targeted treatment along with immunotherapy and recent improvements in radiotherapy and chemotherapy (neoadjuvant-adjuvant capecitabine, cisplatin, gemcitabine) have yielded promising results even in inoperable cases calling for palliation (T4). Thus, individualized treatment must be applied.

Omission of Radiotherapy in Women >60 Years Old After Breast Conserving Surgery for Breast Cancer is Non-Inferior in Terms of Local Recurrence: A Retrospective Cohort Study.

Objective: Local recurrence rate may show no significant differences between women aged 60 and older who receive breast-conserving surgery followed by radiotherapy and those in the same age group who undergo breast-conserving surgery without subsequent radiotherapy. Materials and Methods: Retrospective cohort study from a single practice with median follow-up time 44 months (interquartile range: 16, 82), comparing women older than 60 years old at diagnosis of breast cancer, treated with breast conserving surgery and either receiving or not receiving radiation therapy postoperatively. The primary endpoint was local recurrence difference between the two groups. Results: Local recurrence did not differ significantly between the two groups in terms of radiotherapy or not [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.89-1.02, Fisher's exact test p = 0.388], nor between two age groups with cut-off at 65 years of age (OR: 0.99, 95% CI 0.92-1.07, Fisher's Exact test p = 0.6). Local recurrence also did not differ when subgroups of age (60-65 years and >66 years) were considered. All patients received 5 years of hormonal therapy. Conclusion: Omission of radiotherapy in selected patients is not inferior to radiotherapy after breast conserving surgery in terms of preventing local recurrence.

Hepatic ischemia-reperfusion syndrome and its effect on the cardiovascular system: The role of treprostinil, a synthetic prostacyclin analog.

Hepatic ischemia-reperfusion syndrome has been the subject of intensive study and experimentation in recent decades since it is responsible for the outcome of several clinical entities, such as major hepatic resections and liver transplantation. In addition to the organ's post reperfusion injury, this syndrome appears to play a central role in the dysfunction of distant tissues and systems. Thus, continuous research should be directed toward finding effective therapeutic options to improve the outcome and reduce the postoperative morbidity and mortality rates. Treprostinil is a synthetic analog of prostaglandin I2, and its experimental administration has shown encouraging results. It has already been approved by the Food and Drug Administration in the United States for pulmonary arterial hypertension and has been used in liver transplantation, where preliminary encouraging results showed its safety and feasibility by using continuous intravenous administration at a dose of 5 ng/kg/min. Treprostinil improves renal and hepatic function, diminishes hepatic oxidative stress and lipid peroxidation, reduces hepatictoll-like receptor 9 and inflammation, inhibits hepatic apoptosis and restores hepatic adenosine triphosphate (ATP) levels and ATP synthases, which is necessary for functional maintenance of mitochondria. Treprostinil exhibits vasodilatory properties and antiplatelet activity and regulates proinflammatory cytokines; therefore, it can potentially minimize ischemia-reperfusion injury. Additionally, it may have beneficial effects on cardiovascular parameters, and much current research interest is concentrated on this compound.

Update on current diagnosis and management of anaplastic thyroid carcinoma.

Well-differentiated thyroid carcinoma has a favorable prognosis with a 5-year survival rate of over 95%. However, the undifferentiated or anaplastic type accounting for < 0.2%, usually in elderly individuals, exhibits a dismal prognosis with rapid growth and disappointing outcomes. It is the most aggressive form of thyroid carcinoma, with a median survival of 5 mo and poor quality of life (airway obstruction, dysphagia, hoarseness, persistent pain). Early diagnosis and staging are crucial. Diagnostic tools include biopsy (fine needle aspiration, core needle, open surgery), high-resolution ultrasound, computed tomography, magnetic resonance imaging, [(18)F]fluoro-D-glucose positron emission tomo-graphy/computed tomography, liquid biopsy and microRNAs. The BRAF gene (BRAF-V600E and BRAF wild type) is the most often found molecular factor. Others include the genes RET, KRAS, HRAS, and NRAS. Recent management policy is based on surgery, even debulking, chemotherapy (cisplatin or doxorubicin), radiotherapy (adjuvant or definitive), targeted biological agents and immunotherapy. The last two options constitute novel hopeful management modalities improving the overall survival in these otherwise condemned patients. Anti-programmed death-ligand 1 antibody immunotherapy, stem cell targeted therapies, nanotechnology achievements and artificial intelligence imple-mentation provide novel promising alternatives. Genetic mutations determine molecular pathways, thus indicating novel treatment strategies such as anti-BRAF, anti-vascular endothelial growth factor-A, and anti-epidermal growth factor receptor. Treatment with the combination of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib has been approved by the Food and Drug Administration in cases with BRAF-V600E gene mutations and is currently the standard care. This neoadjuvant treatment followed by surgery ensures a two-year overall survival of 80%. Prognostic factors for improved outcomes have been found to be younger age, earlier tumor stage and radiation therapy. A multidisciplinary approach is necessary, and the therapeutic plan should be individualized based on surveillance and epidemiology end results.

Dental and Skeletal Effects of Herbst Appliance, Forsus Fatigue Resistance Device, and Class II Elastics-A Systematic Review and Meta-Analysis.

Background: Our study aimed to systematically summarize the dentoskeletal effects of Herbst appliance; Forsus fatigue resistance device; and Class II elastics in adolescent Class II malocclusion. Methods: Five databases; unpublished literature; and reference lists were last searched in August 2022. Randomized clinical trials and observational studies of at least 10 Class II growing patients that assessed dentoskeletal effects through cephalometric/CBCT superimpositions were eligible. The included studies quality was assessed with the RoB 2 and ROBINS-I tools. A random-effects model meta-analysis was performed. Heterogeneity was explored with subgroup and sensitivity analyses. Results: Among nine studies (298 patients); two-to-three studies were included in each meta-analysis. Less post-treatment upper incisor retroclination (<2) and no overbite; overjet; SNA; SNB; and lower incisor inclination differences were found between Herbst/Forsus and Class II elastics. No differences in maxilla; condyle; glenoid fossa; and most mandibular changes were found between Herbst and Class II elastics; except for a greater 1.5 mm increase in mandibular length and right mandibular ramus height (1.6 mm) with Herbst. Conclusions: Herbst and Class II elastics corrected the molar relationship; but Herbst moved the lower molars more mesially. Apart from an additional mandibular length increase; no other dental and anteroposterior skeletal difference was found. Forsus was more effective in molar correction; overjet reduction; and upper incisor control than Class II elastics. Trial registration number OSF: 10.17605/OSF.IO/8TK3R.

Retroperitoneal Abscess Formation as a Result of Spilled Gallstones during Laparoscopic Cholecystectomy: An Unusual Case Report.

One of the complications of laparoscopic cholecystectomy for gallstone disease that seems to exceed that of the traditional open method is the gallbladder perforation and gallstone spillage. Its incidence can occur in up to 40% of patients, and in most cases its course is uneventful. However in few cases an abdominal abscess can develop, which may lead to significant morbidity. Rarely an abscess formation due to spilled and lost gallstones may occur in the retroperitoneal space. We herein report the case of a female patient who presented with clinical symptoms of sepsis six months following laparoscopic cholecystectomy. Imaging investigations revealed the presence of a retroperitoneal abscess due to retained gallstones. Due to patient's decision to refuse abscess's surgical drainage, she underwent CT-guided drainage. The 24-month followup of the patient has been uneventful, and the patient remains in good general condition.

Spontaneous perforation of solitary ulcer of transverse colon.

Spontaneous ruptures of the colon and rectum are extremely uncommon clinical entities and always require laparotomy. A 44-year-old female was admitted with a 12-hour history of severe abdominal pain periumbilically and at the right hypochondrium. The patient was immediately transferred to the department of surgery for close surgical observation. Computed tomography (CT) of the entire abdomen performed just before the operation demonstrated thickening of the wall of the ascending colon with pericolic fat stranding. Surgery revealed a perforation at the antimesenteric wall of the transverse colon and segmental colectomy of the transverse colon was performed. The histological evaluation demonstrated a perforated solitary ulcer of the transverse colon. There are only few known etiologic factors concerning spontaneous ruptures of the colon and rectum and usually none of these causative factors can easily be recognised. Their clinical appearance is most of the times acute abdomen and, despite the use of all appropriate diagnostic methods, the diagnosis is usually set postoperatively.

Obstructive ileus due to a giant fibroepithelial polyp of the anus.

Fibroepithelial polyps or hypertrophied anal papillae are essentially skin tags that project up from the dentate line and the junction between the skin and the epithelial lining of the anus. They are usually small in size, but sometimes they become enlarged, causing unexpected medical conditions. An extremely rare case of a giant hypertrophied anal papilla complicated by obstructive ileus is reported. Fibroepithelial anal polyp, despite its size, should be included in the differential diagnosis of a smooth mass located near the anal verge, especially in a patient with a history of chronic anal irritation or infection.

Spermatic cord metastasis presenting as strangulated inguinal hernia - first manifestation of a multifocal colon adenocarcinoma: a case report.

Spermatic cord is a rare metastatic site of colorectal cancer. We herein report a case of spermatic cord metastasis of a previous undiagnosed multifocal colon adenocarcinoma, which was clinically presented as a strangulated groin hernia.

Modifications of coagulation and fibrinolysis mechanism in laparoscopic vs. open cholecystectomy.

BACKGROUND/AIMS: The incidence of thromboembolic complications following laparoscopic cholecystectomy as well as the indication for prophylactic thrombophylaxis is still controversially discussed. The aim of this study is to evaluate the alterations of the coagulation and fibrinolytic mechanism after laparoscopic vs. open cholecystectomy. METHODOLOGY: Forty-five patients, who were submitted to laparoscopic (LC-group, n=30) or open cholecystectomy (OC-group, n=15) were included in the study. The following parameters were measured preoperatively and 24h and 48h postoperatively: platelet count (PLT), prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen (FG), d-dimers (DD) and antithrombin III (AT-III). RESULTS: The preoperative values were within the normal range and did not differ between the two groups. No significant alterations were noted concerning PT and PTT. FG and PLT were significantly increased in both groups at 24h and 48h compared to the baseline values, with no statistical significant difference between them at all time points. D-dimers were significantly elevated at 24h and 48h postoperatively in both groups. The LC-group showed significantly higher AT-III levels at 24h, and significantly lower DD levels at 24h and 48h compared to the OC-group (p < 0.05). CONCLUSIONS: Laparoscopic cholecystectomy seems to induce a lower activation of the hemostatic mechanism compared to open cholecystectomy.

Endoclipping for gastric perforation after endoscopic polypectomy: an alternative treatment to avoid surgery.

A 47-year-old woman underwent endoscopic polypectomy of a villous adenoma in the lesser curvature of the gastric antrum. Shortly after the procedure, she complained of severe abdominal pain. An abdominal x-ray showed air under the diaphragm, suggestive of gastric perforation. On re-endoscopy, the cavity at the site of polypectomy was closed using endoscopically applied metallic clips. She was treated with intravenous hyperalimentation, omeprazole, and antibiotics for 10 days. Ingestion of food was started 10 days after admission, and she was discharged without any complaints. She is free of symptoms on follow-up after 8 months, and endoscopy showed complete healing of the perforation. The procedure is the third described for the stomach in the English literature and emphasizes the use of endoclipping in selected cases of small and well-defined perforations.

Lipid peroxidation and inguinal hernia repair. Tension-free vs. Andrews technique.

AIM OF THE STUDY: To evaluate the early effect of inguinal hernia repair by the tension-free method compared to the conventional Andrew's technique on lipid peroxidation. PATIENTS-METHODS: Thirty-four patients subjected to elective hernia repair were enrolled in the study divided in two groups. Group A (n=18) underwent hernia repair by the tension-free method using a polypropylene mesh. Group B (n=16) underwent hernia repair by the Andrew's technique (i.e. a modification of the Bassini's technique). Venous blood samples were drawn preoperatively and at 12, 24 and 48 h postoperatively. Malondialdehyde (MDA) was estimated by the thiobarbiturate assay. RESULTS: Neutrophil counts were significantly higher in patients of group B compared to group A at 12 and 48 h postoperatively. Concentrations of fibrinogen were similar between the two groups. MDA was significantly higher in patients of group B hours compared to group A at 12, 24 and 48 h postoperatively. Positive correlation was found between neutrophil counts and MDA at 12 h (r: +0.43, P: 0.015) and 48 h (r: +0.496, P: 0.005) but not at 24 h. No correlation was found between serum fibrinogen and MDA. CONCLUSION: Hernia repair by the Andrews's technique elicits a sustained triggering of lipid peroxidation, compared to the tension-free method.

Endoscopic sphincterotomy in patients with "acalculus" cholangitis associated with juxtapapillary diverticula.

BACKGROUND/AIMS: The aim of this study was to investigate patients who underwent endoscopic sphincterotomy for "acalculus" cholangitis associated with juxtapapillary diverticula. METHODOLOGY: In a retrospective study we analyzed 87 patients who underwent endoscopic sphincterotomy for cholangitis; the cholangitis considered "acalculus", when outlining the extra- and intrahepatic bile ducts, we could not observe any intraluminal defect or stricture, and during the clearing of the bile ducts with the balloon, after endoscopic sphincterotomy, there was no evidence of stones, fragments of stones or sludge. Patients who had undergone previous endoscopic sphincterotomy, or who had additional pancreatobiliary diseases were excluded from this study. There were 11 patients with "acalculus" cholangitis associated with juxtapapillary diverticula, and sufficient clinical data available for this study. RESULTS: Nine patients presented pain, fever, and jaundice. In two patients diagnosis was established via the test of abnormal liver biochemistry. Seven patients had positive blood cultures and three of them developed confusion and hypotension. Endoscopic sphincterotomy succeeded in all cases; no evidence of stones, fragments of stones or sludge was recorded during the clearing of bile ducts, after endoscopic sphincterotomy, with the balloon. Five patients presented mild post-endoscopic sphincterotomy complications successfully treated. In the follow-up period, from 4 months to 7 years after endoscopic sphincterotomy, none of the patients developed symptoms of cholangitis. CONCLUSIONS: We recommend endoscopic sphincterotomy in patients with "acalculus" cholangitis associated with juxtapapillary diverticula, despite the absence of obvious obstruction, and the possible morbidity which is inherent with an invasive procedure like endoscopic sphincterotomy.

Endoscopic sphincterotomy in adult hemophiliac patients with choledocholithiasis.

BACKGROUND: The aim of this study was to investigate the risk of bleeding in adult hemophiliac patients undergoing endoscopic sphincterotomy for choledocholithiasis. METHODS: From 1983 to 2002, 7 patients with hemophilia A and two with hemophilia B were referred for endoscopic sphincterotomy and extraction of bile duct stones. The degree of hemophilia was mild in 4 patients, moderate in 3, and severe in two. Pre-admission levels of blood clotting factors ranged from less than 1% to 18%. Levels of the deficient factors were monitored carefully before and after sphincterotomy, and the relevant factor was replaced to achieve 100% activity before and for 24 hours after endoscopic sphincterotomy. OBSERVATIONS: Seven patients had factor replacement every 8 hours, and two received continuous infusions. No patient developed bleeding after sphincterotomy. At discharge, 48 hours after the procedure, patients who had received continuous infusions had a factor level of greater than 90%; those who had received intermittent replacement had levels of greater than 50%. After discharge, the patients were treated with regular infusion of the deficient factor for 15 days. CONCLUSIONS: With adequate preoperative and post-procedure monitoring of clotting factors, meticulous attention to hemostasis during sphincterotomy, careful post-procedure monitoring, and timely replacement therapy, patients with hemophilia can undergo endoscopic sphincterotomy without bleeding complications.

Malignant fibrous histiocytoma of the abdominal cavity: report of a case.

Malignant fibrous histiocytoma (MFH) is a soft-tissue sarcoma originating from fibroblast cells, characterized by a high rate of metastasis or recurrence. This tumor rarely develops in the gastrointestinal tract, with no more than 30 cases described in the literature. We report a case of MFH of the abdominal cavity in a 45-year-old woman who presented with epigastric pain, anorexia, and weight loss. A computed tomography (CT) scan of the abdomen revealed multiple solid tumors in the peritoneal cavity. We performed exploratory laparotomy and found at least 15 solid whitish tumors attached to the wall of the small intestine, as well as to the parietal peritoneum. There were three metastases in the liver. All of the tumors were excised, most of which were about 10 cm in diameter. Histopathological findings indicated a stromal tumor consisting of spindle cells, and immunohistochemical examination of the resected specimens established the definite diagnosis of a pleomorphic MFH. The patient had an uneventful postoperative course and was given adjuvant chemotherapy. She is currently well 2 years after her operation. We review the clinical picture of this tumor in the abdominal cavity, and discuss its diagnosis, pathogenesis, and treatment.

Congenital web of the common bile duct in association with cholelithiasis.

Congenital web formations are extremely rare anomalies of the extrahepatic biliary tree. The age at presentation and the clinical symptomatology of these anomalies depend on the grade of the biliary obstruction. We report a case of a common bile duct septum in association with cholelithiasis in a 30-year-old woman. The diagnosis was made on preoperative magnetic resonance cholangiopancreatography (MRCP) and confirmed with intraoperative cholangiography. Because all known causes of acquired web formation were excluded, a congenital origin of the web was assumed. The patient was treated with a hepaticoduodenostomy above the level of the septum. The embryological aspects of this rare anomaly are described.