Bile Duct Cancer: Preoperative Evaluation and Management

Cholangiocarcinomas (CCAs) are malignant tumors that can develop anywhere along the biliary tree. Almost 10% of cholangiocarcinomas arise from the intra-hepatic bile ducts (iCCA); 50–60% from the bifurcation of the hepatic duct (perhilar cholangiocarcinoma, pCCA); and 20–30% from the distal bile duct (dCCA). The 7th edition of the AJCC staging system, released in 2010, divides the tumors into two major categories: perihilar (pCCA) and distal (dCCA) cholangiocarcinoma, given the differences in anatomy of the bile duct and consideration of local factors related to resectability. There are separate histological classifications for intrahepatic and extrahepatic cholangiocarcinoma. The majority of CCAs (90%) are well or moderately differentiated adenocarcinomas. Other features include invasiveness with early neural, perineural, periductal and lymphatic infiltration (more than 50% of cases at diagnosis) and longitudinal subepithelial infiltration along the wall of the bile duct up to 2 cm proximally and 1 cm distally. In this chapter the extrhepatic bile duct cancers are analyzed

Survival to amputation in pre-antibiotic era: a case study from a Longobard necropolis (6th-8th centuries AD)

The Longobard necropolis of Povegliano Veronese dates from the 6th to the 8th centuries AD. Among the 164 tombs excavated, the skeleton of an older male shows a well-healed amputated right forearm. The orientation of the forearm fracture suggests an angled cut by a single blow. Reasons why a forearm might be amputated include combat, medical intervention, and judicial punishment. As with other amputation cases reported in literature, this one exhibits both healing and osteoblastic response. We argue that the forelimb stump morphology suggests the use of a prosthesis. Moreover, dental modification of RI2 shows considerable wear and smoothing of the occlusal surface, which points to dental use in attaching the prosthesis to the limb. Other indications of how this individual adjusted to his amputated condition includes a slight change in the orientation of the right glenoid fossa surface, and thinning of right humeral cortical bone. This is a remarkable example in which an older male survived the loss of a forelimb in pre-antibiotic era. We link archaeological remains found in the tomb (buckle and knife) with the biological evidence to show how a combined bioarchaeological approach can provide a clearer interpretation of the life history of an individual

Liver Trauma

Objective: The aim of this section is to assess the evolution in the management of liver injuries during the last two decades

Intrahepatic Cholangiocarcinoma

Aim: The authors give a complete overview on this disease from epidemiology to treatment

A Stepwise Proposal for Low-Grade Hemorrhoidal Disease: Injection Sclerotherapy as a First-Line Treatment and Rubber Band Ligation for Persistent Relapses

Outpatient treatments are actually the techniques of choice in the management of low-grade hemorrhoidal disease. Among these, rubber band ligation (RBL) and injection sclerotherapy (IS) are the most frequently performed. Both techniques are used, without one having been determined to be superior over the other. We analyzed the studies that compare these two techniques in terms of efficacy and safety in order to offer a proposal for treatment choice. RBL seems to be most efficient in terms of symptom resolution for second-degree hemorrhoidal disease and equal or superior for treatment of third-degree disease. However, IS offers lower rates of severe post-operative pain and minor complications. Since outpatient treatments are offered to patients as painless options that allow a prompt recovery, we propose a stepwise protocol using 3% polidocanol or aluminum potassium sulfate and tannic acid IS as the first treatment option, as it has less complications, followed by RBL in cases of relapse

Leukemia inhibitory factor protects cholangiocarcinoma cells from drug-induced apoptosis via a PI3K/AKT-dependent Mcl-1 activation

Cholangiocarcinoma is an aggressive, strongly chemoresistant liver malignancy. Leukemia inhibitory factor (LIF), an IL-6 family cytokine, promotes progression of various carcinomas. To investigate the role of LIF in cholangiocarcinoma, we evaluated the expression of LIF and its receptor (LIFR) in human samples. LIF secretion and LIFR expression were assessed in established and primary human cholangiocarcinoma cell lines. In cholangiocarcinoma cells, we tested LIF effects on proliferation, invasion, stem cell-like phenotype, chemotherapy-induced apoptosis (gemcitabine+cisplatin), expression levels of pro-apoptotic (Bax) and anti-apoptotic (Mcl-1) proteins, with/without PI3K inhibition, and of pSTAT3, pERK1/2, pAKT. LIF effect on chemotherapy-induced apoptosis was evaluated after LIFR silencing and Mcl-1 inactivation. Results show that LIF and LIFR expression were higher in neoplastic than in control cholangiocytes; LIF was also expressed by tumor stromal cells. LIF had no effects on cholangiocarcinoma cell proliferation, invasion, and stemness signatures, whilst it counteracted drug-induced apoptosis. Upon LIF stimulation, decreased apoptosis was associated with Mcl-1 and pAKT up-regulation and abolished by PI3K inhibition. LIFR silencing and Mcl-1 blockade restored drug-induced apoptosis. In conclusion, autocrine and paracrine LIF signaling promote chemoresistance in cholangiocarcinoma by up-regulating Mcl-1 via a novel STAT3- and MAPK-independent, PI3K/AKT-dependent pathway. Targeting LIF signaling may increase CCA responsiveness to chemotherapy

Surgical and Interventional Management of Complications Caused by Pancreatitis

Acute pancreatitis has a broad clinical spectrum: from mild, self-limited disease to fulminant illness resulting in multi-organ failure leading to a prolonged clinical course with up to 30% mortality in case of infected necrosis. Management of local complications such as pseudocysts and walled-off necrosis may vary from clinical observation to interventional treatment procedures. Gram negative bacteria infection may develop in up to one-third of patients with pancreatic necrosis leading to a clinical deterioration with the onset of the systemic inflammatory response syndrome and organ failure. When feasible, an interventional treatment is indicated. Percutaneous or endoscopic drainage approach are the first choices. A combination of minimally invasive techniques (step-up approach) is possible in patients with large or multiple collections. Open surgical treatment has been revised both in the timing and in the operating modalities in the last decades. Since 1990s, the surgical treatment of infected necrosis shifted to a more conservative approach. Disruption of the main pancreatic duct is present in up to 50% of patients with pancreatic fluid collections. According to the location along the Wirsung, treatment may vary from percutaneous drainage, endoscopic retrograde pancreatography with sphincterectomy or stenting to traditional surgical procedures. Patients may suffer from vascular complications in up to 23% of cases. Tissue disruption provoked by lipolytic and proteolytic enzymes, iatrogenic complications during operative procedures, splenic vein thrombosis, and pseudoaneurysms are the pathophysiological determinants of bleeding. Interventional radiology is the first line treatment and when it fails or is not possible, an urgent surgical approach should be adopted. Chylous ascites, biliary strictures and duodenal stenosis are complications that, although uncommon and transient, may have different treatment modalities from non-operative, endoscopic to open surgery

Management of Acute and Chronic Pancreatitis

Pancreatitis is a major public health issue worldwide. There is geographical variation in the burden of acute and chronic pancreatitis (CP). Globally, the age-standardized prevalence rate increased from 1990 to 2017. Acute pancreatitis (AP) is now one of the most common reasons for hospitalization with a gastrointestinal condition. The essential requirements for the management of AP are accurate diagnosis, appropriate triage, high-quality supportive care, monitoring for and treatment of complications, and prevention of relapse. Clinicians should be aware of the time course and the best management of AP, identifying which patient will have a severe course allowing earlier triage to an intensive care unit and earlier initiation of effective therapy. CP is a pathologic fibroinflammatory syndrome of the pancreas in individuals with genetic, environmental, and other risk factors who develop persistent pathologic responses to parenchymal injury or stress. Diagnosing the underlying pathologic process early in the disease course and managing the syndrome to change the natural course of disease and minimize adverse disease effects are the managing paradigm. In this review, we consider recent changes in the management of acute and CP, as well as common misunderstandings and areas of ongoing controversy

Minimally invasive spleen-preserving distal pancreatectomy: real-world data from the italian national registry of minimally invasive pancreatic surgery

Aim: Minimally invasive distal pancreatectomy has become the standard of care for benign and low malignant lesions. Spleen preservation in this setting has been proposed to reduce surgical trauma and long-term sequelae. The aim of the current study is to present real-world data on indications, techniques, and outcomes of spleen-preserving distal pancreatectomy (SPDP). Methods: Patients who underwent SPDP and distal pancreatectomy with splenectomy (DPWS) were extracted from the 2019-2022 Italian National Registry for Minimally Invasive Pancreatic Surgery (IGoMIPS). Perioperative and pathological data were collected. Results: One hundred and ten patients underwent SPDP and five hundred and seventy-eight underwent DPWS. Patients undergoing SPDP were significantly younger (56 vs. 63.5 years; P < 0.001). Seventy-six percent of SPDP cases were performed in six out of thirty-four IGoMIPS centers. SPDP was performed predominantly for Neuroendocrine Tumors (43.6% vs.23.5%; P < 0.001) and for smaller lesions (T1 57.6% vs. 29.8%; P < 0.001). The conversion rate was higher in the case of DPWS (7.6% vs. 0.9%; P = 0.006), even when pancreatic cancer was ruled out (5.0% vs. 0.9%; P = 0.045). The robotic approach was most commonly used for SPDP (50.9% vs. 29.7%; P < 0.001). No difference in postoperative outcomes and length of stay was observed between the two groups, as well as between robotic and laparoscopic approaches in the SPDP group. A trend toward a lower rate of postoperative sepsis was observed after SPDP (0.9% vs. 5.2%; P = 0.056). In 84.7% of SPDP, splenic vessels were preserved (Kimura procedure) without an impact on short-term postoperative outcomes. Conclusion: In this registry analysis, SPDP was feasible and safe. The Kimura procedure was prevalent over the Warshaw procedure. The typical patient undergoing SPDP was young with a neuroendocrine tumor at an early stage. Robotic assistance was used more frequently for SPDP than for DPWS

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients