Edoardo Virgilio

Is EUS-FNA of solid-pseudopapillary neoplasms of the pancreas as a preoperative procedure really necessary and free of acceptable risks?

BACKGROUND Solid-pseudopapillary neoplasms (SPNs) of the pancreas are infrequent tumors since, as of 2014, only 2744 patients have been described. Its rarity, unclear histogenesis, pleomorphic aspect on radiology (cystic, solid or mixed) and unpredictable biological behavior with an insidious high-grade malignant potential make SPN difficult to recognize preoperatively even in its target patient population which is predominantly composed of young women (about 87% of cases). METHODS Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) showed to improve the preoperative diagnostic yield for this tumor and obviate the risks formerly given by percutaneous biopsy. RESULTS In light of our experience, such a procedure could not be so innocuous as generally acknowledged. CONCLUSION We report the first case of rupture of pancreatic SPN following EUS-FNA and entertain both the actual and potential complications ensuing from this type of mishap.

Solitary left axillary metastasis after curative surgery for right colon cancer

mouth. GFPO is postulated to arise at the pharyngo-oesophageal junction in the muscle deficient Laimer-Haeckermann triangle when a flap of mobile, redundant submucosa prolapses distally, slowly enlarging over time. Endoscopic differentiation of bulky GFPO lesions from oesophageal sarcoma or leiomyoma may be difficult. Misguided attempts at radical longitudinal resection of the oesophagus should be avoided. Endoscopic resection is appropriate in selected, generally smaller lesions though care must be taken with potentially large feeding vessels. An open left cervical approach provides access to larger lesions with minimal morbidity.

Lymph node ratio is a stronger prognotic factor than microsatellite instability in colorectal cancer patients: Results from a 7 years follow-up study

BACKGROUND The presence of high microsatellite instability (MSI-H) in colorectal cancers has been generally associated with better survival, opposite an increased ratio between metastatic lymph-nodes and nodes sampled in the specimen (LNR) has been associated with a worse outcome. The study aims to detect the incidence and prognostic significance of MSI and LNR in a consecutive series of 119 colorectal cancers. METHODS 119 consecutive colorectal cancer patients undergone resection at our Department were enrolled from 2000 to 2004. The MSI status has been evaluated by amplification of target sequences. The LNR has been calculated and patients stratified into 4 groups on the basis of the ratio values. Clinical/pathological data were collected and analyzed; the overall, disease free and disease specific survivals were analyzed by the Kaplan-Meier and Cox regression analyses (mean follow-up: 81 months). RESULTS MSI-H was detected in 11.7% of the cases and patients were compared with the microsatellite stable (MSS) group. We observed a higher prevalence of right colon localizations (p 0.01) and locally advanced tumors (p 0.0012) in the MSI-H subgroup. Kaplan-Meier analysis documented no significant difference comparing MSS patients vs MSI-H, although the latter showed a better survival trend (p ns); worse survivals were observed according with the LNR stratification (p < 0.0001). Multivariate analysis documented a statistical value associated with the LNR sub-groups in relationship with survival. CONCLUSION According to our results the MSI-H status was associated with particular features (right locations/locally advanced tumors). The results of a long-term follow-up indicate a trend for better survival in MSI-H vs MSS patients. Notably, an increased LNR is associated with worse survivals, both at the univariate and multivariate analysis, displaying this ratio as the strongest prognostic factor of cancer-related survival.

Mesogastrium recurrence as expression of the fifth metastatic route of gastric cancer

causing its internalization and degradation. Hepcidin levels are upregulated by iron intake and inflammation and markedly downregulated by iron deficiency anemia. Insufficient hepcidin production, regardless of iron overload, is also the key pathogenic feature of most types of HH. Because of the low hepcidin levels in the two conditions, iron deficiency anemia and HH are both characterized by macrophages with little or no iron. The failure of vascular wall macrophages to retain iron in cases of inherited iron overload accompanied by a lower production of hepcidin may prevent progression and destabilization of atherosclerotic plaque [10]. Indeed, hepcidin has been recently confirmed to represent a positive regulator of atherosclerotic plaque destabilization via regulating iron homeostasis in macrophages [12]. A recent meta-analysis involving studies on single nucleotide polymorphisms has found a significant association between CHD risk and H63D mutation; however no association has been shown between other HFE gene variants and CHD risk [13]. Notably, C282Y/H63D heterozygous may develop a milder form of hemochromatosis [14], and are still be able to produce hepcidin, whose values are in fact slightly higher than normal individuals (without HFE mutations) [15]. The different behaviour of C282Y/H63D heterozygous (who retain a relative ability to increase hepcidin production in response to iron, even if still inadequate for iron stores) as compared to C282Y homozygous (who produce very low hepcidin levels), likely related to the different impact of the two mutations on HFE function, may influence the different relationship with CHD risk. Therefore, the controversial results of the association between HH and CHD does not exclude a key role for iron in atherogenesis in subjects without inherited deficiencies of hepcidin. Future studies should be conducted to find out whether iron depletion or hepcidin regulators might reduce CHD risk.

Prognostic significance of 18q LOH in sporadic colorectal carcinoma

Identification of molecular alterations with implication for prognosis and sensibility to chemotherapeutic agents represents a great challenge in colorectal carcinoma treatment. Controversial results have been reported on prognostic value of chromosome 18q loss. Ninety-seven unselected patients with sporadic colorectal carcinoma Stage II and III were investigated for loss of heterozygosity at 18q D18S58 and D18S61 loci. Molecular alterations were correlated with clinicopathological data and survival. 18q loss of heterozygosity (LOH) was present in 56 per cent cases of carcinoma and was not related either to the clinicopathological characteristics of the patients or to prognosis. However, patients with LOH at locus D18S61 showed a more favorable prognosis. This finding was especially true for Stage II and untreated carcinoma. Survival was not influenced by the status of D18S58 locus. In our series, LOH at chromosome 18q does not seem to predict an unfavorable outcome. It seems of special interest the benefit that D18S61 loss of heterozygosity confers to untreated patients and patients with Stage II colon carcinoma.

Detection of cancer cells and tumor markers in gastric lavage of patients with gastric cancer: Do these findings have a clinicopathological significance and oncological implication?

Although decreasing in the incidence over the last years, currently gastric adenocarcinoma represents the second cause of cancer related-death worldwide. Further knowledge and novel therapies are desperately needed in order to make the prognosis of these patients more acceptable. Infact, even though in recent years numerous staging parameters have been largely studied and unanimously recognized for their clinical and prognostic value, today too many shadows still exist around the capacity to predict exactly the natural history or post-treatment behavior of this cancer even among patients of the same stage. This study has identified the presence of isolated cancer cells as well as tumor markers (CEA, Ca 19.9, Ca 72.4 and Ca 50) from the gastric lavage of patients affected by gastric adenocarcinoma. Such findings led to the hypothesis that endoluminal exfoliation of neoplastic cells and the release of their products (tumor markers) into the gastric juice might be an expression of neoplastic behavior as well as aggressive malignancy. Should this hypothesis become a reality, some important progress could be made in the knowledge, staging, prediction as well as management and follow-up of this inauspicious type of cancer.

Is entirely conservative management a correct strategy for hemodynamically stable patient with a grade IV blunt pancreatic injury

The first case of pancreatic injury was described by Travers in 1827, and long-held but uncertain opinions still surround this formidable disease. We commend Dr. Pata and colleagues for the notable information introduced into the nonoperative management for grade III blunt pancreatic injury [1] and raise one question with interest: As of the most recent follow-up, did you find any ‘‘upstream’’ chronic pancreatitis in this group of patients treated conservatively? Recently, we grappled with the case of a 20-year-old woman who sustained a road traffic accident. She was vigilant and hemodynamically stable all of the time, although a multidetector double-contrast computed tomography scan showed complete pancreatic transection to the right of the superior mesenteric vessels with no associated duodenal injury and a 4.7 cm hematoma in segment VI of the liver. The serum amylase level was 1097 U/l. Considering both the aforementioned hemodynamic stability and grade IV pancreatic disruption, we elected to manage the patient conservatively with bowel rest, total parenteral nutrition, gabexate mesylate, octreotide, meropenem, teicoplanin, and paracetamol. The patient made a full recovery on conservative treatment, resuming oral intake on day 10 and becoming dischargeable on day 23 after admission. At the 18-month follow-up, she maintained a satisfactory healthy state and magnetic resonance pancreatography revealed atrophy to the pancreatic body-tail together with dilated Wirsung and secondary ducts. In this era of damage control management, many endeavors have provided a unanimous consensus for an algorithm to follow for trauma to the spleen, liver, and kidney but not for the pancreas [2]. Each case seems unique and thus hinders us from drawing the basic outlines for a uniform diagnostic and therapeutic algorithm. Currently, conservative management of stable adults and children with blunt pancreatic injury is the norm in cases of low-grade (I–II) injuries, as such lesions resolve spontaneously within 4 to 10 days. Controversies arise in the presence of a main pancreatic duct injury, which is recognized as the main determinant of morbidity and mortality [3]. In the pediatric literature some successful cases of nonoperative care are described for high-grade (III–IV) injuries [4]; in the adult literature, conversely, an entirely expectant management for grade III injuries was first described in 2009 [1] and, except for some cases treated by ancillary techniques, is still unprecedented for grade IV injuries. Historical treatments for grade IV pancreatic injuries include distal pancreatectomy, pancreaticoenterostomy, debridement with surgical drainage, percutaneous drainage, and pancreatic duct stenting [5]. We addressed a case of grade IV blunt pancreatic injury with a nonoperative strategy, avoiding any surgical, endoscopic, or interventional procedure during both the early and later period of observation. We encourage use of this approach for stable patients with class III–IV pancreatic lesions to augment information about this topic and tailor the best clinical practice for each case. Our caveat is that the clinical status of the patient, rather than the grade of pancreatic injury, should be the principal determinant to guide the diagnostic and therapeutic decisions. Surgery P. Mercantini E. Virgilio (&) T. Bocchetti A. Kazemi Nava V. Ziparo Department of General Surgery 1, II Faculty of Medicine La Sapienza of Rome, Hospital S. Andrea, Rome, Italy e-mail: aresedo1992@yahoo.it

Analyzing Gastric Lavage of Gastric Cancer Patients: A Prospective Observational Study on Cytopathology and Determination of Intragastric CEA, CA 19.9, CA 72.4, and CA 50.

Objectives: To investigate gastric lavage (GL) cytopathology and immunometric analysis as novel clinicopathologic and prognostic parameters for gastric cancer (GC). Study Design: In 38 patients with gastric adenocarcinoma, we performed a cytopathologic analysis and an immunometric assay of GL using four tumor markers (CEA, CA 19.9, CA 72.4, and CA 50). The intragastric tumor marker levels were compared with a control group consisting of 41 non-GC patients to determine a statistically significant cutoff value. Results: GL cytopathology demonstrated the presence of cancer cells in 13 (34.2%) of the 38 GC patients: such a finding correlated to the parameters pT and pN with a statistically significant validity (p < 0.0267 and p < 0.0306, respectively). Measurement of intragastric CA 19.9 and CA 50 attained a statistically significant cutoff value (p < 0.002 and p < 0.0096, respectively), which was invalidated by the low sensitivity of the ROC curve analysis. Conclusions: In contrast to determination of its tumor markers, GL cytopathology correlated well with pT and pN staging parameters. Should this and other features be corroborated by future studies, the GL cytology test could be routinely used to detect aggressive types of GC even at early stages and result in important progress in the knowledge, staging, prediction, as well as management and follow-up of this inauspicious type of cancer.

Giant Hepatic Artery Aneurysm Associated with Immunoglobulin G4-Related Disease Successfully Treated Using a Liquid Embolic Agent

Copyright

Commentary on “Clinical Characteristics and Adequate Treatment of Familial Adenomatous Polyposis Combined with Desmoid Tumors”

We commend Jung et al. [1] on their noteworthy effort to describe the clinicopathological features, risk factors, and outcomes of familial adenomatous polyposis (FAP) patients with desmoid tumors (DTs). In this regard, we would like to stress a particular and disturbing aspect of this disease, which is the potentially ambiguous role of surgery towards young FAP patients with colorectal cancer (CRC). In fact, in these patients, the post-surgical development of massive intra-abdominal DTs represents a fatal event in the vast majority of cases, as discussed in more detail hereafter. Recently, we performed total proctocolectomy in a 28-year-old nulliparous FAP-girl (APC mutation 3′ to codon 3238) who developed a cancerous polyp of the rectum. The patient did well after the intervention until, after 6 months, she developed a pregnant looking abdomen, even though she was not pregnant. A computed tomography scan showed a solid mass of the mesentery measuring 28 cm×21 cm, which occupied the entire abdominal cavity encasing the superior mesenteric vessels and both common iliac arteries: a radiological diagnosis of giant mesenteric DT was notched (Fig. 1). Due to the irresectable nature of the lesion, the patient was referred to a specialized center for intestinal and multivisceral transplantation, but, during evaluation she became rapidly aggravated until death. Fig. 1. Coronal (A) and sagittal (B) view of the stage IV intra-abdominal desmoid tumor occupying the entire abdominal cavity and encasing vital vascular structures Despite being extremely rare in the general population, intra-abdominal DTs (also known as mesenteric fibromatosis) represent the most frequent cause of death in patients affected with FAPhaving undergone total proctocolectomy [2]. Although histologically benign and clinically non-metastasizing, these monoclonal myofibroblastic proliferations can show a highly aggressive local behavior, achieving massive size, infiltrating major vessels and causing severe complications, such as bowel ischemia and obstruction, fistulae with peritonitis, bleeding and venousthromboembolism [2]. Young nulliparous women using contraceptives with history of colectomy are at higher risk of development [2]. Pathobiology is poorly understood: consequently, their behavior is unpredictable and there is no standardized medical orsurgical treatment [1]. A valuable measure in management of this kind of lesion was provided in 2005 by Church et al. [3] who proposed a clinical staging system based on tumorsize, growth and the presence ofsymptoms and complications. While stage I, II, and III are amenable to several modalities of treatment (antiestrogens, nonsteroidal anti-inflammatory drugs,selective tyrosine kinase inhibitor, chemotherapy, and surgical resection),stage IV tumors (larger than 20 cm, rapidly growing and severely symptomatic such as our case) are characterized by higher morbidity and mortality rates: indeed, any medical treatmentseemsto be in vain astoo much time is required for any type of benefit and surgical resection is often impossible for the encasement of vital vessels [1]. Currently, advanced unresectable mesenteric DTs are the fourth most common indication for intestinal transplant intervention worldwide [4]. However, not all of these patients arrive at transplantation (as in our case) and the 5-year survival rate does not exceed 70% [2]. Greater knowledge of giant inoperable mesenteric DTs is needed, and, in particular, young FAP patients should be thoroughly informed on the risk of this ominous event when undergoing colectomy for CRC and carefully followed-up.