Tumor immune-gene expression profiles and peripheral immune phenotypes associated with clinical outcomes of locally advanced pancreatic cancer following FOLFIRINOX.

BACKGROUND: A comprehensive analysis of peripheral immune cell phenotypes and tumor immune-gene expression profiles in locally advanced pancreatic cancer patients treated with neoadjuvant chemotherapy in a phase II clinical trial was carried out. METHODS: Patients were treated with neoadjuvant modified folinic acid, fluorouracil, irinotecan hydrochloride, oxaliplatin (mFOLFIRINOX) followed by surgery and adjuvant gemcitabine at the Asan Medical Center. Correlations between survival outcomes and baseline peripheral immune cells and their changes during preoperative chemotherapy were analyzed. Patients who had surgery were divided into two groups according to achievement of disease-free survival >10 months (achieved versus failed). Differential expression and pathway analysis of immune-related genes were carried out using the Nanostring platform, and immune cells within the tumor microenvironment were compared by immunohistochemistry. RESULTS: Forty-four patients were treated in the phase II clinical trial. Higher baseline CD14+CD11c+HLA-DR+ monocytes (P = 0.044) and lower Foxp3+CD4+ T cells (P = 0.02) were associated with poor progression-free survival of neoadjuvant mFOLFIRINOX. During the preoperative chemotherapy, PD-1 T cells significantly decreased (P = 0.0110). Differential expression and pathway analysis of immune-genes from the resected tumor after neoadjuvant treatment revealed transforming growth factor-ß pathway enrichment and higher expression of MARCO (adjusted P < 0.05) associated with early recurrence. Enrichment of the Th1 pathway and higher peritumoral CD8+ T cells (P = 0.0103) were associated with durable disease-free survival from surgery (>10 months) following neoadjuvant mFOLFIRINOX. CONCLUSIONS: Our results identify potential immune biomarkers for locally advanced pancreatic cancer and provide insights into pancreatic cancer immunity.

Reversible cerebral vasoconstriction syndrome: a comprehensive systematic review.

OBJECTIVE: We aimed to analyze clinical characteristics, treatment patterns, and prognosis of patients with reversible cerebral vasoconstriction syndrome (RCVS). MATERIALS AND METHODS: Two investigators independently searched PubMed and EMBASE, and 191 cases were included in this study. Information regarding demographics, triggering factors, brain imaging findings, treatment modalities, recurrence, and clinical outcome was collected. RESULTS: The mean age of the patients was 39.9 years, and 155 (81.2%) were female. The most common triggering factor for RCVS was an exposure to vasoactive substances (41.4%), followed by pregnancy/postpartum (20.9%), and sexual intercourse (10.5%). Multifocal stenosis (84.0%) and beading shape (82.4%) were the leading abnormal findings on angiography, while cerebral ischemic lesions (47.6%) and cerebral hemorrhage (mainly subarachnoid hemorrhage) (35.1%) were the main findings on brain computed tomography (CT)/magnetic resonance imaging (MRI). Calcium channel blockers (nimodipine/verapamil) were the most commonly used medications (44.5%) in the treatment of RCVS. Multivariate analysis identified that RCVS was precipitated by trauma/surgery/procedure (hazard ratio (HR): 3.29, 95% confidence interval (CI) (1.21-8.88), p=0.019), and presence of aphasia/neglect/apraxia during the acute phase of the disease (HR: 3.83, 95% CI (1.33-11.05), p=0.013) were found to be the two independent risk factors for residual neurological deficit after RCVS. CONCLUSIONS: In our systematic review, vasoactive substances were the most frequent triggers for RCVS, which was most commonly accompanied by angiographic findings of multifocal stenotic lesions. Patients with RCVS precipitated by trauma or surgical procedures and those with focal cortical deficits had a higher risk of residual neurological deficits, and these patients should closely be monitored.

Molecular network pathways and functional analysis of tumor signatures associated with development of resistance to viral gene therapy.

Replication-competent attenuated herpes simplex viruses have proven effective in killing many cancer cell lines. However, determinants of resistance to oncolytic therapy are mostly unknown. We developed viral therapy-resistant cells and examined changes in gene-expression pattern compared with therapy-sensitive parental cells. Colon cancer cell line HT29 and hepatoma cell line PLC5 were exposed to increasing concentrations of virus G207. Therapy-resistant cells were isolated and grown in vitro. Tumorigenicity was confirmed by ability of cell lines to form tumors in mice. Human Genome U133A complementary DNA microarray chips were used to determine gene-expression patterns, which were analyzed in the context of molecular network interactions, pathways and gene ontology. In parental cell lines, 90-100% of cells were killed by day 7 at 1.0 multiplicity of infection. In resistant cell lines, cytotoxicity assay confirmed 200- to 400-fold resistance. Microarray analysis confirmed changes in gene expressions associated with resistance: cell surface proteins affecting viral attachment and entry, cellular proteins affecting nucleotide pools and proteins altering apoptotic pathways. These changes would decrease viral infection and replication. Our study identifies gene-expression signatures associated with resistance to oncolytic viral therapy. These data provide potential targets to overcome resistance, and suggest that molecular assays may be useful in selecting patients for trial with this novel treatment.

Surgical outcomes and prognostic factors for ampulla of Vater cancer.

BACKGROUND AND AIMS: The prognosis for patients with ampulla of Vater cancer is better than other periampullary cancers. The aim of the present study is to determine the clinicopathologic factors predictive of survival and recurrence in patients with ampulla of Vater cancer. MATERIAL AND METHODS: From 1991 to 2008, we identified and reviewed 78 patients with ampulla of Vater cancer retrospectively. Clinicopathologic factors possibly influencing survival and recurrence were statistically analyzed. RESULTS: Pancreaticoduodenectomy was performed in 68 patients and 2 patients underwent transduodenal ampullectomy. Hospital mortality was 2.6%. The 5-year survival rates following resection were 59.9%. Univariate analysis for overall survival revealed that total bilirubin greater than 5 mg/dl, ulcerative tumors, differentiation, and pancreatic invasion were significant prognostic factors. Recurrence occurred in 31 patients. Univariate analysis for disease-free survival revealed that total bilirubin greater than 5mg/dl, preoperative biliary drainage, tumor differentiation, and stage were statistically significant. Multivariate analysis revealed that tumor differentiation was an independent prognostic factor for recurrence. The presence of lymph node metastasis did not affect overall survival significantly in this study. However, two or more metastatic lymph nodes significantly affect disease-free survival. CONCLUSIONS: Pancreaticoduodenectomy is a safe surgical procedure with acceptable long-term survival for ampulla of Vater cancer. Pancreaticoduodenectomy with lymph node dissection might control lymph node spread and enhance survival outcome.

Successful vaginal delivery following laparoscopic abdominal wall reconstruction in an adult survivor of an omphalocele without prior surgical repair: report of a case.

We report the case of a successful vaginal delivery following laparoscopic abdominal wall reconstruction in an adult survivor of an omphalocele without prior surgical repair. Untreated omphaloceles are rare in adulthood. A 30-year-old female patient presented with a large anterior abdominal wall defect due to an untreated omphalocele, who expressed a desire to have a baby in the near future. A laparoscopic herniorrhaphy was performed with a double-layered expanded polytetrafluoroethylene (ePTFE, Gore-Tex) mesh. The patient delivered a full-term healthy baby vaginally 2 years after surgical repair of the omphalocele.

Systemic immune response after open versus laparoscopic cholecystectomy in acute cholecystitis: a prospective randomized study.

OBJECTIVE: Laparoscopic surgery is thought to reduce the postoperative immunologic effects of surgical trauma. The aim of this study is to evaluate the influence of surgical trauma on systemic inflammation and the immune response in acute cholecystitis. MATERIAL AND METHODS: Thirty-three patients with acute calculous cholecystitis were assigned to laparoscopic cholecystectomy (LC, n=18) or open cholecystectomy (OC, n=15). Blood samples were obtained preoperatively and on postoperative day 1 (24 h after surgery) and day 3 (72 h after surgery), and blood concentration of C-reactive protein (CRP), leukocyte subpopulations, as well as levels of tumor necrosis factor-alpha (TNF-alpha) ex vivo secretion by peripheral blood mononuclear cells (PBMCs) were measured in both groups. RESULTS: Hospitalization was significantly shorter in the LC group than in the OC group (LC group: 3.7+/-1.2 days versus OC group: 6.3+/-2.7 days, p=0.010). There was no postoperative morbidity in the LC group, but two patients in the OC group had postoperative complications. Postoperative TNF-alpha ex vivo secretion by PBMCs and PBMC counts in the OC group were significantly lower than those in the LC group (p=0.002). The CRP level declined by postoperative day 3, but was significantly less in the OC group than in the LC group (p<0.001). Postoperative monocyte counts significantly decreased in the OC group compared with those in the LC group (p=0.001). CONCLUSIONS: A laparoscopic approach appears to cause less surgical trauma and immunosuppression than open surgery in patients with acute cholecystitis.

[Prognostic factors in the evaluation of colorectal liver metastases]. / Prognostische Faktoren kolorektaler Lebermetastasen.

The liver is the most common site for the clinical appearance of hematogenous metastases from colorectal cancers. It is now accepted that surgical resection represents not only the best treatment but also a potentially curative one. Extensive resections are being performed routinely in many centers around the world. Practical problems that have arisen are the classification and staging of patients subjected to such treatments. Traditional staging would group all patients with hepatic colorectal metastases in stage IV. In the current paper, we discuss the evolution of this classification according to our understanding of prognostic implications. We first discuss classifying these patients according to clinical prognostic factors, separating preoperative factors from those available only postoperatively. A discussion follows of the practical use of such clinical classification systems in daily care. We then suggest the potential future evolution of prognostic considerations, including the use of nomograms, molecular pathologic variables, and biologic scanning and the implications of response to neoadjuvant chemotherapy.

Laparoscopic-assisted resection of ileal lipoma causing ileo-ileo-colic intussusception.

Adult intussusception is rare, and the majority of cases has an underlying cause that requires surgical resection. We report a case of a 39 yr-old man with ileo-ileo-colic intussusception caused by ileal lipoma that was successfully managed by a laparoscopic-assisted surgical maneuver. Using a three-cannula technique, ileo-colic intussusception was reduced laparoscopically. Then, through a 4-cm transverse incision in the right lower quadrant abdomen, ileo-ileal intussusception was reduced manually, and a resection of the tumor-bearing ileal segment and end-to-end anastomosis was performed extracorporeally. Although the role of laparoscopy in managing intussusception is not clearly defined, laparoscopy may be an alternative approach to the surgical treatment of adult intussusception in selected cases.

Correlation of esophageal lengths with measurable external parameters.

Previous data for esophageal lengths are based on age related groups or cadaveric examination, both of which are improper for application to various individualized procedures. Because of the variability in height for any given age and longer length in vivo, individualized approximation is needed. Thus, we measured various anatomical levels of the esophagus using a flexible endoscope and correlated these data with measurable external body intervals. The mean esophageal length was 40.92 +/- 2.79, which is longer than the length derived from cadaveric examinations. Also, esophageal lengths which correlated better with height than any other body intervals, could be calculated from the following equation. Esophageal length from the upper incisors to the esophagogastric junction (L) can be expressed: L = 0.242 x height (Ht) + 2.078 cm (P = 0.000, R2 = 0525). The data from our study indicate that esophageal length can be reliably predicted using external body parameters before employing various procedures.

A case of primary T-cell lymphoma of the duodenum.

Primary malignant lymphoma located in the duodenum is a rarity. A case of primary lymphoma of the duodenum in a 27-year-old man, in which the 2 discrete masses of duodenal bulb and the second portion with pancreatic head invasion was found, is reported here. Immunohistochemical evaluation of the present case showed that lymphoma cells expressed the T-cell markers MT1 and UCHL1. Treatment consisted of pancreaticoduodenectomy followed by antineoplastic chemotherapy.