Hepatic Arterial Infusion of Chemotherapy for Advanced Hepatobiliary Cancers: State of the Art.

Liver functional failure is one of the leading causes of cancer-related death. Primary liver tumors grow up mainly in the liver, and thus happens for liver metastases deriving from other organs having a lower burden of disease at the primary site. Systemic chemotherapy usually offers a modest benefit in terms of disease control rate, progression-free survival, and overall survival at the cost of a significant percentage of adverse events. Liver malignancies are mostly perfused by the hepatic artery while the normal liver parenchyma by the portal vein network. On these bases, the therapeutic strategy consisting of hepatic arterial infusion (HAI) of chemotherapy takes place. In literature, HAI chemotherapy was applied for the treatment of advanced hepatobiliary cancers with encouraging results. Different chemotherapeutic agents were used such as Oxaliplatin, Cisplatin, Gemcitabine, Floxuridine, 5-Fluorouracil, Epirubicin, individually or in combination. However, the efficacy of this treatment strategy remains controversial. Therefore, this review aims to summarize the current knowledge on this approach from different points of view, such as techniques, drugs pharmacology and pharmacokinetics, and clinical outcomes for advanced hepatobiliary cancers.

Mast Cells Positive for c-Kit Receptor and Tryptase Correlate with Angiogenesis in Cancerous and Adjacent Normal Pancreatic Tissue.

BACKGROUND: Mast cells (MCs) contain proangiogenic factors, in particular tryptase, associated with increased angiogenesis in several tumours. With special reference to pancreatic cancer, few data have been published on the role of MCs in angiogenesis in both pancreatic ductal adenocarcinoma tissue (PDAT) and adjacent normal tissue (ANT). In this study, density of mast cells positive for c-Kit receptor (MCDP-c-KitR), density of mast cells positive for tryptase (MCDPT), area of mast cells positive for tryptase (MCAPT), and angiogenesis in terms of microvascular density (MVD) and endothelial area (EA) were evaluated in a total of 45 PDAT patients with stage T2-3N0-1M0. RESULTS: For each analysed tissue parameter, the mean ± standard deviation was evaluated in both PDAT and ANT and differences were evaluated by Student's t-test (p ranged from 0.001 to 0.005). Each analysed tissue parameter was then correlated to each other one by Pearson t-test analysis (p ranged from 0.01 to 0.03). No other correlation among MCDP-c-KitR, MCDPT, MCAPT, MVD, EA and the main clinical-pathological characteristics was found. CONCLUSIONS: Our results suggest that tissue parameters increased from ANT to PDAT and that mast cells are strongly associated with angiogenesis in PDAT. On this basis, the inhibition of MCs through tyrosine kinase inhibitors, such as masitinib, or inhibition of tryptase by gabexate mesylate may become potential novel antiangiogenetic approaches in pancreatic cancer therapy.

Reorganization of the endoscopic activity of Cancer Institutes during phase II of the Covid-19 emergency.

After the lockdown during the emergency phase of the Covid-19 pandemic, we have to deal with phase 2, a period of uncertain duration, with a controlled and progressive return to normalization, in which we need to reconcile our work and our movements with the presence of the virus on our territory. Digestive endoscopic activity is a high-risk transmission procedure for Covid-19. The measures put in place to protect healthcare personnel and patients are stressful and "time-consuming" and lead to a reduction in the number of endoscopic procedures that can be performed. In this scenario, the Oncological Institutes are forced to make a rigorous selection of patients to undergo endoscopic examinations and treatments, according to lists of exceptional priorities, in order to guarantee cancer patients and subjects at high risk of developing digestive tumors, a preferential diagnostic and therapeutic process, protected from contagion risks. For this purpose, cuts and postponing times of endoscopic performances are here proposed, which go beyond the guidelines of scientific societies and have little evidences in the literature. These changes should be applied limited to this exceptional period and in proportion to the capacity of each operating unit in order to meet the demands of the patients.

Successful endoscopic treatment of gastric phytobezoar: A case report.

INTRODUCTION: Gastric bezoars are a rare condition associated with situations of gastric dysmotility and prior gastric surgery, though sometimes they can present without any risk factor. We describe the first successful treatment in medical literature of a large gastric bezoar in the outpatient setting through endoscopic fragmentation. CASE PRESENTATION: A 76-year-old man was referred to our outpatient endoscopy clinic because of dyspepsia and epigastric pain. Upper GI endoscopy with a standard endoscope revealed a 10-cm-diameter gastric phytobezoar with necrotic pressure ulcer of the angulus. We fragmentized the bezoar into smaller pieces, with complete dissolution and without any complication. The patient was then promptly discharged home with a medical therapy. Follow-up endoscopy at 6 months showed the total disappearance of any residual fibers. DISCUSSION: Different types of bezoars are described in literature, of which phyto- and trychobezoars are the most frequent. They can be absolutely asymptomatic or can arise with epigastric pain, pressure ulcer bleeding, gastrointestinal perforation or small bowel obstruction. The treatment is debated though endoscopic removal or fragmentation with the help of Coca-Cola lavages has showed the best success rate. The main experiences in literature concern hospitalized patients or describe treatment techniques which require overnight stays. An effective and rapid treatment in the outpatient setting is described in our experience, without short- or long-term complications. CONCLUSION: The endoscopic fragmentation of large gastric bezoars in the outpatient setting is safe with a good clinical course.

Covered nitinol stents for the treatment of esophageal strictures and leaks.

AIM: To compare 2 different types of covered esophageal nitinol stents (Ultraflex and Choostent) in terms of efficacy, complications, and long-term outcome. METHODS: A retrospective review of a consecutive series of 65 patients who underwent endoscopic placement of an Ultraflex stent (n = 33) or a Choostent (n = 32) from June 2001 to October 2009 was conducted. RESULTS: Stent placement was successful in all patients without hospital mortality. No significant differences in patient discomfort and complications were observed between the Ultraflex stent and Choostent groups. The median follow-up time was 6 mo (inter-quartile range 3-16 mo). Endoscopic reintervention was required in 9 patients (14%) because of stent migration or food obstruction. No significant difference in the rate of reintervention between the 2 groups was observed (P = 0.8). The mean dysphagia score 1 mo after stent placement was 1.9 +/- 0.3 for the Ultraflex stent and 2.1 +/- 0.4 for the Choostent (P = 0.6). At 1-mo follow-up endoscopy, the cover membrane of the stent appeared to be damaged more frequently in the Choostent group (P = 0.34). Removal of the Choostent was possible up to 8 wk without difficulty. CONCLUSION: Ultraflex and Choostent proved to be equally reliable for palliation of dysphagia and leaks. Removal of the Choostent was easy and safe under mild sedation.

Endoscopic gastrostomy for enteral nutrition in neurogenic dysphagia: Application of a nasogastric tube or percutaneous endoscopic gastrostomy.

Enteral nutrition can be administered via a nasogastric tube or, in selected patients, via a percutaneous endoscopic gastrostomy. In patients with neurogenic dysphagia, the choice of nutritional administration, and above all the timing, are crucial. Our aim was to retrospectively assess the impact of new guidelines for percutaneous endoscopic gastrostomy insertion adopted since January 2002 and compare them with our previous experience. From January 1992 to June 2007, 285 gastrostomies (168 M, 117 F) were positioned in our institute. We analysed 232 patients (139 M, 93 F) in whom a percutaneous endoscopic gastrostomy was applied for neurogenic dysphagia: Group A (from January 1992 to December 2001) consisting of 174 patients; Group B (from January 2002 to June 2007) consisting of 58 patients. The percutaneous endoscopic gastrostomy was positioned in all the cases with neurogenic dysphagia after a period of not less than 3 weeks of nutrition by nasogastric tube. A total of 6 major complications (2.3 %) occurred, almost all in group A. The mortality rate (3 patients, 2%) correlated with the complications in group A. In cases of neurogenic dysphagia we believe that greater methodological rigour in the multidisciplinary decision-making process, and a period of about 6-8 weeks' nutrition by nasogastric tube after the acute neurological damage may be useful to ensure a better prognostic evaluation of the patient and hence of the indications for percutaneous endoscopic gastrostomy.

Endoscopic management of large colorectal polyps.

OBJECTIVES: The optimal treatment for large colorectal polyps (LCPs) is still a controversial issue. The aim of this study was to evaluate the safety and effectiveness of endoscopic polypectomy (EP) of colorectal polyps >or=2 cm in size. PATIENTS AND METHODS: One hundred fifty-one EP LCPs were performed over a period of 7 years. Diathermal snare was used for pedunculated and pseudopedunculated polyps and endoscopic mucosal resection (EMR) or biopsy forceps polypectomy for sessile and flat polyps. The resected polyps were recovered and collected for histology. At scheduled follow-up visits 1, 3, 6, and 12 months after polypectomy, complications and recurrences were recorded in all patients. RESULTS: Fifteen polyps were located in the rectum, 84 in the sigmoid colon, 11 in the descending colon, four in the splenic flexure, 11 in the transverse colon, 11 in the hepatic flexure, seven in the ascending colon and eight in the cecum. Fifty-six polyps were sessile, 54 pedunculated, 25 pseudopedunculated, and 16 flat. At histology, most of polyps (131) were adenomas (nine with adenocarcinoma in situ). Five were invasive polypoid carcinomas and required colonic resection. Immediate bleeding occurred in ten patients (7.6%) and it was stopped by endoscopic hemoclips (7), epinephrine injection (1), or surgery (2). There were three perforations (2.3%; all polypoid carcinomas), managed endoscopically (1) or surgically (2). Delayed bleeding occurred in two patients (1.5%) and was treated by endoscopic diathermy and hemoclips (1) or surgery (1). During follow-up, six (4.6%) incompletely excised polyps and three (2.3%) relapses in the site of previous EP were detected and endoscopically removed. CONCLUSION: EP is relatively safe and effective for benign-appearing LCPs.

Laparoscopy-assisted endoscopic mucosal resection in the colon: a preliminary report.

Endocopic mucosal resection of flat villous tumours or giant polyps (> 3 cm) may give rise to local complications such as haemorrhage or perforation because of the very thin wall of the colon, above all in the right half. Our aim was to evaluate whether laparoscopy-assisted endoscopic excision of flat villous tumours or giant polyps (> 3 cm) can be safely performed, avoiding critical septic complications and can also help in the selection of patients to be submitted to colonic resection without increasing morbidity or mortality. The procedure is a new minimally invasive therapeutic approach in selected cases with large, sessile or awkwardly located polyps. Unlike other techniques such as polypectomy, endoscopic mucosal resection completely removes the affected mucosa by resecting through the middle or deeper part of the submucosa. Another purpose of the procedure is to obtain specimens for accurate pathological staging. Our experience consisted in the treatment of two patients, one of whom with a laterally spreading tumour of the transverse colon with the suck and cut cap-assisted technique, and one with a large sessile polyp of the caecum with the lift and cut technique. The patients presented no complications and no recurrence was observed during the subsequent follow-up.

[Extra-ampullary duodenal neoplasms]. / Le neoplasie duodenali in sede extra-ampollare.

The authors report on twelve cases of non-ampullary duodenal neoplasm and remark the rarity of this pathology. According to the literature, the traditional endoscopy is the mainstay diagnostic test, because of aspecific digestive symptoms, but the authors stress the importance of the "longue" endoscopy or endoscopy integrated with duodenography in non-responders patients who had non-diagnostic traditional endoscopy for neoplasm. Duodeno-cephalo-pancreatectomy and segmentary duodenal resection are proposed by tumor site. Better results for prognosis can be obtained only with an early diagnosis and radical surgical therapy, because of chemotherapy and radiotherapy don't improve survival.

Large bowel multiple tumours.

The medical records of all patients with colorectal cancer seen at the "G. Marinaccio" Department of Surgery in Bari between 1997 and 2004 were examined. Cases included in the study met the criteria advocated by Warren and Gates and Moertel et al. Over such period we operated on 103 patients with colon neoplasms, mostly males (64 patients) and aged over 65 (64 patients). Both palliative and radical operations were performed either as elective treatment or as emergency surgery; in some of the latter cases the diagnosis of neoplasm was made casually following the final histological test on the operative specimen. Ten cases of multiple malignant tumours were recorded, corresponding to 9.7%; in particular 1 synchronous-metachronous tumour (0.97%), 3 synchronous tumours (2.7%) and 6 metachronous tumours (5.8%) were observed; two of the metachronous tumours were detected in the same patient and one in a patient that had previously been operated on for a synchronous carcinoma, thus making a total of 8 patients in all. It is concluded that full examination of the colon in all patients presenting with primary colorectal cancer is mandatory and that, in the light of this experience and recent reports in the literature, this should be done by pre- or perioperative colonoscopy. Colonoscopy not only provides accurate detection of lesions, but also allows the surgeon to perform polypectomies, thereby obviating the need for extending surgery at the time of resection of the coexisting cancer. In conclusion, we recommend preoperative colonoscopy for all patients who present non-obstructive colorectal neoplasms.

[The acute cholecystitis: the operative timing for the laparoscopic approach]. / La colecistite acuta: il timing operativo con l'approccio laparoscopico.

The aim of this study is to evaluate the results of early cholecystectomy in patients with acute cholecystitis. In the past, acute cholecystitis was a contraindication to laparoscopic cholecystectomy because of the greater risk of injury to the biliary duct, but acute gallbladder inflammation was a contraindication to open cholecystectomy, too. With greater experience and new technology, laparoscopic cholecystectomy is today the gold standard in the treatment of acute cholecystitis, in empyema and gangrenous cholecystitis. In recent years, attention has turned to surgical timing, rather than surgical management--open versus laparoscopy--because there is no advantage in delaying cholecystectomy for acute cholecystitis. In our experience, we always choose laparoscopic technique in all the patients without general contraindications to mini-invasive surgery and operate as soon as possible in a patient with unfavourable conditions. We believe that the patient must be quickly stabilized with preoperative medical procedures, and surgical treatment must be performed within 72-96 hours after the onset of symptoms. During this period, laparoscopic approach allows a reduction of operative time, operative risk and the conversion rate with medical and economic advantages.

[Gastric anisakidosis: personal experience]. / L'anisakidosi gastrica: esperienza personale.

Anisakidosis is a parasitic disease of the human gastrointestinal tract caused by ingestion of marine nematode larvae such as anisakis simplex or, rarely, Pseudoterranova, present in raw or undercooked fish. Frequent sites of involvement by anisakis are the stomach, small intestine, rarely the colon, or the peritoneum, liver, pancreas, lung and tonsils, anisakidosis is a self-limiting disease; the symptoms arise 12-24 hours after ingesting raw fish and include nausea, diarrhoea, and severe abdominal pain, but also anaphylactic reactions. At the site of penetration, anisakis causes marked oedema, eosinophilic infiltration and granuloma formation. There are haematological abnormalities such as marked leukocytosis of the peripheral blood, eosinophilia, and positive PCR and serum antibodies to the larva's surface antigens. The diagnosis of anisakidosis can be made by endoscopy, radiology and US, but the disease is often diagnosed at surgical intervention. In the gastric form of anisakidosis, EGIDS has both a diagnostic role and a therapeutic one because it is possible to remove the worm using biopsy forceps. We report on one case of gastric anisakidosis, in a women, hospitalised for intense epigastric pain and vomiting after ingesting raw fish. She underwent gastroscopy. A worm was extracted from the gastric mucosa using biopsy forceps. This was followed by clinical improvement. The worm was identified by its macroscopic and microscopic characteristics as an anisakis larva. At laboratory examination, marked leukocytosis and eosinophilia of the patient's peripheral blood were observed 3-4 days after ingestion of anisakis.

[Gastrointestinal stromal tumors: current issues]. / Tumori stromali gastrointestinali: attuali problematiche.

Gastrointestinal stromal tumours are rare neoplasms originating from the connective tissue of the digestive tract and constitute most of the non-epithelial primitive digestive tumours, with a percentage incidence of less than 1%. The term itself was first used in 1983 by Mazur and Clark to identify a heterogeneous group of tumours, all of them histologically characterised by hyperplastic fused cells, not necessarily leiomuscular ones, but even neural ones. The original stem cell has not been identified yet, but such tumours constantly present the expression of the surface antigens CD34 and CD117 which can be determined immunohisto-chemically. US endoscopy and fine needle aspiration with subsequent immunohistochemical analysis and study of c-kit gene mutation afford the best diagnostic accuracy. Current research is focused mainly on primary cells, probably the cells of Cajal, and on the study of the biological behaviour of gastrointestinal stromal tumours, which can be postulated by assessing several parameters, the most accurate of which seems to be the mitotic index. More recently, the possible therapeutic use of a tyrosine kinase inhibitor has been studied in tumours expressing the c-kit gene. Our experience is based on the histopathological and immunohistochemical study of 11 submucosal tumours (1 liposarcoma, 2 leiomiomas, and 8 gastrointestinal stromal tumours) out of a total of 75 submucosal tumours diagnosed. In the majority of cases a generic diagnosis of submucosal tumour was obtained with oesophagogastro-duodenoscopy and a surgical resection was then performed because of the symptoms. Only in 4 cases was the neoplasm found occasionally in the course of surgery for other reasons. The definitive diagnosis of gastrointestinal stromal tumour, as currently defined, was made only postoperatively by analysis of the histopathological and immunohistochemical findings. In all cases we evaluated the same parameters, i.e. actin, vimentine, S100, CD34, CD117, and Ki67, and confirmed constant high positivity for CD34 and above all for CD117. Even in the absence of unfavourable prognostic indicators, all patients are regularly followed-up.

[Granular cell tumors of the colon. Clinical case and review of the literature]. / Tumori a cellule granulose del colon. Caso clinico e revisione della letteratura.

Abrikossoff's tumours are better known as granular cell tumours because of the typical microscopic aspect of their cytoplasm. They are uncommon neoplasms, probably of neurogenic origin, typically subepithelial and often benign. Rarely, they may be localised in the digestive tract, where they are mostly asymptomatic and tend to be discovered incidentally during endoscopic examinations indicated for other diseases. Histological examination with immunohistochemical staining usually yields the definitive diagnosis. Most authors agree as to the indication for endoscopic resection because of the possible, though rare, aggressive biological behaviour of these tumours. In the present paper we report on a case of granular cell tumour of the caecum, endoscopically resected and staining positively at the immunohistochemical search for the S100 protein.