Minimally Invasive Surgical Approaches for Pancreatic Adenocarcinoma: Recent Trends.

BACKGROUND: Pancreatic resection for cancer represents a real challenge for every surgeon. Recent improvements in laparoscopic experience, minimally invasive surgical techniques and instruments make now the minimally invasive approach a real "triumph." There is no doubt that minimally invasive surgery has replaced with great success conventional surgery in many fields, including surgical oncology. METHODS AND RESULTS: However, its progress in pancreatic resection for adenocarcinoma has been dramatically slow. Recent evidence supports the notion that minimally invasive distal pancreatectomy is safe and feasible and that is becoming the procedure of choice mainly for benign or low-grade malignant lesions in the distal pancreas. On the other side, minimally invasive pancreatoduodenectomy has not yet been widely accepted and there is enormous skepticism when applied for pancreatic head adenocarcinoma. In this review, we summarize the current evidence on the potential applications of minimally invasive surgical approaches for this aggressive, heterogeneous, and enigmatic type of cancer. CONCLUSIONS: Moreover, the potential future applications of these approaches are discussed with the hope to improve the quality of life as well as the survival rates of pancreatic cancer patients.

From Clinical Standards to Translating Next-Generation Sequencing Research into Patient Care Improvement for Hepatobiliary and Pancreatic Cancers.

Hepatobiliary and pancreatic (HBP) cancers are associated with high cancer-related death rates. Surgery aiming for complete tumor resection (R0) remains the cornerstone of the treatment for HBP cancers. The current progress in the adjuvant treatment is quite slow, with gemcitabine chemotherapy available only for pancreatic ductal adenocarcinoma (PDA). In the advanced and metastatic setting, only two targeted drugs have been approved by the Food & Drug Administration (FDA), which are sorafenib for hepatocellular carcinoma and erlotinib for PDA. It is a pity that multiple Phase III randomized control trials testing the efficacy of targeted agents have negative results. Failure in the development of effective drugs probably reflects the poor understanding of genome-wide alterations and molecular mechanisms orchestrating therapeutic resistance and recurrence. In the post-ENCODE (Encyclopedia of DNA Elements) era, cancer is referred to as a highly heterogeneous and systemic disease of the genome. The unprecedented potential of next-generation sequencing (NGS) technologies to accurately identify genetic and genomic variations has attracted major research and clinical interest. The applications of NGS include targeted NGS with potential clinical implications, while whole-exome and whole-genome sequencing focus on the discovery of both novel cancer driver genes and therapeutic targets. These advances dictate new designs for clinical trials to validate biomarkers and drugs. This review discusses the findings of available NGS studies on HBP cancers and the limitations of genome sequencing analysis to translate genome-based biomarkers and drugs into patient care in the clinic.

Identification of novel genes by whole-exome sequencing can improve gastric cancer precision oncology.

AIM: By identifying cancer driver genes involved in tumorigenesis, whole-exome sequencing (WES) analyses enable the development of robust biomarkers and novel therapeutic targets to reach precision oncology. PATIENTS & METHODS: WES analyses were performed in matched gastric cancer-normal gastric tissues from two patients. We compared genes highlighted with those of a database and recent WES/whole-genome sequencing studies. RESULTS: We identified 32 highlighted gastric cancer genes, two of these (DEFB118 and RNF43) may provide future potential clinical implications. CONCLUSION: Definitive evidence on extensive genetic heterogeneity suggests the need for large-scale next-generation sequencing studies to validate gastric cancer driver genes catalog. This list represents the foundation for developing genome-based biomarkers to guide precision gastric cancer treatment.

Sentinel node navigation in gastric cancer: new horizons for personalized minimally invasive surgical oncology?

Complete (R0) resection and regional lymph nodes (LNs) dissection represent undoubtedly the basic surgical tools for patients with gastric cancer. It is reported that the LN metastasis rate in patients with early gastric cancer (EGC) is approximately 15-20%. Therefore, the innovative clinical application of sentinel node navigation surgery (SNNS) for EGC might be able to prevent unnecessary LN dissection as well as to reduce significantly the volume of gastric resection. Recent evidence suggests that double tracer methods appear superior compared to single tracer techniques. However, the researchers' interest is now focused on the identification of new LN detection methods utilizing sophisticated technology such as infrared ray endoscopy, fluorescence imaging and near-infrared technology. Despite its notable limitations, hematoxylin-eosin is still considered the mainstay staining for assessing the metastatic status of LNs. In this review, we summarize the current evidences and we provide the latest scientific information assessing safety, efficacy and potential limitations of the innovative sentinel node (SN) navigation technique for gastric cancer. We try also to provide a "view" towards a future potential application of personalized minimally invasive surgery in gastric cancer field.

Surgical management of hydatid liver disease.

BACKGROUND: large retrospective clinical study describing the long-term experience of a single center in the surgical management of liver echinococcosis in an endemic area. METHODS: 232 patients were operated for liver hydatid disease between 1978 and 2012. Seventy-three patients (Group A) underwent a radical procedure (total pericystectomy or hepatectomy), while 145 (Group B) were treated with a more conservative method (partial cystectomy, with external drainage, omentoplasty or capitonnage) and 14 (Group C) received a combination of total and partial cystectomies. Morbidity, mortality, post-operative complications and recurrence rates in the long-term setting were retrospectively evaluated. RESULTS: Group A patients were treated with zero mortality and a morbidity rate of 10.95%. No recurrence was documented. In Group B, mortality reached 2.76%, (p = 0.153 compared to Group A) morbidity 24.13% (p = 0.021) and there were 10 cases of relapse (6.9%) at three-year complete follow-up (p = 0.989). Extrahepatic sites of disease were not uncommon. DISCUSSION: radical surgical procedures were better tolerated by patients and yielded better results in terms of recurrence rates.

Unusual locations of hydatid disease: a 33 year's experience analysis on 233 patients.

Hydatid disease is caused by the tapeworm Echinococcus granulosus and it is an endemic parasitic disease of the Mediterranean countries. Although the liver is the most involved organ by this disease, hydatidosis can be found anywhere in the human body. Rare forms of location may pose diagnostic and therapeutic dilemmas. Herein we report our experience with unusual located hydatid disease diagnosed and treated at our center the last 33 years. A total of 233 patients were treated for echinococcosis (91 males: 39% and 142 females: 61%) between 1980 and 2013 at our center. 18 of them (7, 8%) with uncommon located hydatid disease, were analyzed retrospectively. 18 patients (8 males and 10 females) were presented with unusual location of hydatid disease in our series. Two of them had only extrahepatic cysts (0, 9%). A total of 64 hydatid cysts with unusual location were analyzed. The most prevalent extrahepatic sites were peritoneal cavity and spleen. Total cystectomy with or without tube drainage or omentopexy was performed for hydatid cysts of the peritoneal cavity in our series. Splenectomy was performed in all cases of splenic hydatidosis. The mean time of post operative stay was 16, 3 days (range 7-35 days), morbidity 11% and mortality 5, 4%. Although echinococcosis is found most often in the liver and lungs, it seems that any organ can be involved by this zoonotic disease. The operating surgeon must always consider the possibility of unusual location of echinococcal cyst when dealing with patients with cystic mass in endemic areas, because any misinterpretation may result in unfavorable outcomes.

Non-secreting benign glucagonoma diagnosed incidentally in a patient with refractory thrombocytopenic thrombotic purpura: report of a case.

Thrombotic thrombocytopenic purpura (TTP) is a rare hematologic disorder, which may be idiopathic or secondary to a variety of diseases. However, there are very few reports of TTP in the context of pancreatic neoplasms. We report a case of relapsing TTP after initial treatment with plasmapheresis, corticosteroids, and rituximab, in a 59-year-old woman. During diagnostic work-up, a pancreatic lesion 35 × 25 mm in size was discovered incidentally and splenopancreatectomy was performed. The pathological diagnosis was benign glucagonoma. The hematological symptoms resolved completely after the procedure and 3 years later, the patient is well with no sign of recurrence of TTP or glucagonoma. To our knowledge, this represents the first documented case of a non-secreting benign pancreatic neuroendocrine tumor (glucagonoma) associated with TTP that is refractory to standard treatment.

Perirenal PEComa: Computed Tomography Findings and Differential Diagnosis.

The World Health Organization defines perivascular epithelioid cell tumors (PEComas) as mesenchymal tumors and tumor-like conditions composed of epithelioid cells with a perivascular distribution. These tumors may show benign or malignant histology and/or biological behavior. However, the pathological features of malignancy may not correlate with biologic aggressiveness, and the criteria for malignancy are not clearly defined. Abdominopelvic PEComas are very rare and have been reported in various locations, including kidney, liver, pancreas, gastrointestinal tract, genitourinary tract, peritoneum, and retroperitoneum. Cross-sectional imaging techniques, including computed tomography (CT) may play an important role in the accurate detection and characterization of these tumors. We present the third case of an extremely rare PEComa with perirenal location, discuss CT findings and differential diagnosis.

An uncommon, life-threatening, traumatic hematoma in the neck area.

It is well known that blunt neck trauma, when compared to a penetrating injury in the same anatomical area, is very rare. We report a case of an 81-year-old Caucasian woman with a blunt life-threatening neck trauma due to a bully goat. Although rare, direct evaluation should always be done in these cases because any misinterpretation may result in unfavorable outcomes. We have to highlight that close medical attention and prompt surgical treatment should be always considered in order to avoid dramatic consequences.

Potential of antibody-drug conjugates and novel therapeutics in breast cancer management.

Progress in the treatment of cancer over the past decade has been slow. Targeting a mutated gene of an individual patient tumor, tumor-guided agents, and the first draft of the human genome sequence have created an overenthusiasm to achieve personalized medicine. However, we now know that this effort is misleading. Extreme interpatient and intratumor heterogeneity, scarce knowledge in how genome-wide mutational landscape and epigenetic changes affect transcriptional processes, gene expression, signaling transduction networks and cell regulation, and clinical assessment of temporary efficacy of targeted drugs explain the limitations of these currently available agents. Trastuzumab and a few other monoclonal antibodies or small-molecule tyrosine kinase inhibitors (TKIs) represent an exception to this rule. By blocking ligand-binding receptor in patients with human epidermal growth factor receptor 2 (HER2) amplification and overexpression, trastuzumab added to chemotherapy in HER2-positive patients has been proven to provide significant overall survival benefit in both metastatic and adjuvant settings. Lapatinib, a small-molecule dual inhibitor (TKI) of both HER2 and EGFR (epidermal growth factor receptor) pathways, has an antitumor activity translated into progression-free survival benefit in HER2-positive metastatic patients previously treated with a taxane, an anthracycline, and trastuzumab. Despite these advances, ~25% of patients with HER2-positive breast cancer experience recurrence in the adjuvant setting, while in the metastatic setting, median survival time is 25 months. In this review, we discuss the safety, efficacy, and limitations of the trastuzumab emtansine (T-DM1) conjugate in the treatment of HER2-positive metastatic breast cancer. We also highlight Phase III randomized trials, currently underway, using either the T-DM1 conjugate or various combinations of monoclonal antibodies and TKIs. Moreover, in contrast with all these agents developed on the basis of "central dogma" of simplified reductionist transcription and single gene-phenotype linear relationship, we summarize the emerging, amazing era of next-generation, transcriptional circuitry and intracellular signaling network-based drugs guided by the latest advances in genome science and dynamics of network biology.

BMI and lymph node ratio may predict clinical outcomes of gastric cancer.

AIM: BMI and the lymph node (LN) ratio can affect short- and long-term outcomes of patients with gastric cancer. PATIENTS & METHODS: This study includes 104 consecutive patients with gastric adenocarcinoma who underwent curative gastrectomy divided in two groups: overweight group (group A) and normal weight group (group B). RESULTS: We found that 53.4% of our patients were overweight (group A). The overall rate of postoperative complications was 16.3%, while mortality was 1%. Statistical analyses revealed that postoperative morbidity was significantly higher in group A (p < 0.05). Long-term survival was significantly higher in group B. Cox regression showed a statistically significant correlation between higher BMI and poor long-term survival after curative gastrectomy. Multivariate analysis has identified age and the LN ratios as independent prognostic factors of survival. CONCLUSION: In this retrospective analysis, BMI and LN ratio were independently associated with survival in patients with gastric cancer. Further studies are needed to confirm our findings.

Gastric volvulus and wandering spleen: a rare surgical emergency.

Gastric volvulus is a rare but potentially life-threatening clinical entity due to possible gastric necrosis. A wandering spleen may also be associated with gastric volvulus. Patients presenting with the triad epigastralgia, vomiting followed by retching, and difficulty or inability to pass a nasogastric tube into the stomach are likely to have gastric volvulus. The operating surgeon should include this rare entity in the differential diagnosis when dealing with a patient with such a clinical profile. Herein, we present a case of gastric volvulus associated with a wandering spleen in a 28-year-old Caucasian woman and we provide a brief review of the literature on this issue.

Successful Nonoperative Management of Spontaneous Splenic Hematoma and Hemoperitoneum due to CMV Infection.

Introduction. Spontaneous splenic hematoma or splenic rupture due to CMV infection in immunocompetent adults is rare and life-threatening. Case Report. Herein we report a rare case of spontaneous splenic hematoma and hemoperitoneum due to CMV infection in a 23-year-old Caucasian male in whom conservative management was successful. Conclusion. Spontaneous splenic hematoma and spontaneous splenic rupture are extremely rare conditions during primary CMV infection. Though rare, they must be always considered by the operating surgeon, because any misinterpretation may result in unfavorable outcomes.