The microsatellite instability (MSI) phenotype may constitute an important biomarker for patient response to immunotherapy, particularly to anti-programmed death-1 inhibitors. MSI is a type of ...genomic instability caused by a defect in DNA mismatch repair (MMR) proteins, which is present mainly in colorectal cancer and its hereditary form, hereditary nonpolyposis colorectal cancer. Gastrointestinal stromal tumor (GIST) development is associated with activating mutations of KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor α (PDGFRA), which are oncogenes that predict the response to imatinib mesylate. In addition to KIT/PDGFRA mutations, other molecular alterations are important in GIST development. In GISTs, the characterization of the MSI phenotype is scarce and the results are not consensual. The present study aimed to assess MSI in a series of 79 GISTs. The evaluation of MSI was performed by pentaplex polymerase chain reaction comprising five markers, followed by capillary electrophoresis. The expression of MMR proteins was evaluated by immunohistochemistry. Regarding the KIT/PDGFRA/B-Raf proto-oncogene, serine/threonine kinase molecular profile of the 79 GISTs, 83.6% of the tumors possessed KIT mutations, 10.1% had PDGFRA mutations and 6.3% were triple wild-type. The mutated-PDGFRA cases were associated with gastric location and a lower mitotic index compared with KIT-mutated and wild-types, and these patients were more likely to be alive and without cancer. MSI analysis identified 4 cases with instability in one marker, however, additional evaluation of normal tissue and immunohistochemical staining of MMR proteins confirmed their microsatellite-stable nature. The results of the present study indicated that MSI is not involved in GIST tumorigenesis and, therefore, cannot serve as a biomarker to immunotherapy response in GIST.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The use of laparoscopy for the treatment of gastric cancer suffered some resistance among surgeons around the world, gaining strength in the past decade. However, its oncological safety and technical ...feasibility remain controversial.
To describe the results from the clinical and anatomopathological point of view in the comparative evaluation between the surgical videolaparoscopic and laparotomic treatments of total gastrectomy with linphadenectomy at D2, resection R0.
Retrospective analyses and comparison data from patients submitted to total gastrectomy with D2 linphadenectomy at a sole institution. The data of 111 patients showed that 64 (57,7%) have been submitted to laparotomic gastrectomy and 47 (42,3%) to gastrectomy entirely performed through videolaparoscopy. All variables related to the surgery, post-operative follow-up and anatomopathologic findings have been evaluated.
Among the studied variables, videolaparoscopy has shown a shorter surgical time and a more premature period for the introduction of oral and enteral nourishment than the open surgery. As to the amount of dissected limph nodes, there has been a significant difference towards laparotomy with p=0,014, but the average dissected limph nodes in both groups exceed 25 nodes as recommended by the JAGC. Was not found a significant difference between the studied groups as to age, ASA, type of surgery, need for blood transfusion, stage of the disease, Bormann classification, degree of differentiation, damage of the margins, further complications and death.
The total gastrectomy with D2 lymphadenectomy performed by laparoscopy presented the same benefits known of laparotomy and with the advantages already established of minimally invasive surgery. It was done with less surgical time, less time for re-introduction of the oral and enteral diets and lower hospitalization time compared to laparotomy, without increasing postoperative complications.
Chronic diseases such as chagasic megaesophagus (secondary to Chagas' disease) have been suggested as etiological factors for esophageal squamous cell carcinoma; however, the molecular mechanisms ...involved are poorly understood.
We analyzed hotspot
gene mutations in a series of esophageal squamous cell carcinomas associated or not with chagasic megaesophagus, as well as, in chagasic megaesophagus biopsies. We also checked for correlations between the presence of
mutations with patients' clinical and pathological features.
The study included three different groups of patients: i) 23 patients with chagasic megaesophagus associated with esophageal squamous cell carcinoma (CM/ESCC); ii) 38 patients with esophageal squamous cell carcinoma not associated with chagasic megaesophagus (ESCC); and iii) 28 patients with chagasic megaesophagus without esophageal squamous cell carcinoma (CM).
hotspot mutations in exons 9 and 20 were evaluated by PCR followed by direct sequencing technique.
mutations were identified in 21.7% (5 out of 23) of CM/ESCC cases, in 10.5% (4 out of 38) of ESCC and in only 3.6% (1 case out of 28) of CM cases. In the CM/ESCC group,
mutations were significantly associated with lower survival (mean 5 months), when compared to wild-type patients (mean 2.0 years). No other significant associations were observed between
mutations and patients' clinical features or
mutation profile.
This is the first report on the presence of
mutations in esophageal cancer associated with chagasic megaesophagus. The detection of
mutations in benign chagasic megaesophagus lesions suggests their putative role in esophageal squamous cell carcinoma development and opens new opportunities for targeted-therapies for these diseases.
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Background/purpose
Laparoscopic pancreatic surgery is gaining acceptance and clear advantages have been demonstrated in distal resection. Total pancreaticoduodenectomy (TPD) combines the operative ...steps of distal pancreatectomy and pancreaticoduodenectomy, but facilitates reconstruction and lowers the risk of common complications by avoiding the need for a pancreatic anastomosis. The aim of this report is to analyse the feasibility of laparoscopic total pancreaticoduodenectomy, with and without spleen and pylorus preservation.
Methods
Two patients underwent laparoscopic TPD for pancreatic intraductal mucinous neoplasm and endocrine tumors. Total splenopancreaticoduodenectomy (TSP) and pylorus- and spleen-preserving total pancreaticoduodenectomy (PSPTP) were performed.
Results
The two procedures were successfully completed laparoscopically. PSPTP was more time-consuming (420 vs. 360 min) and had an increased risk of hemorrhage (600 vs. 200 ml) compared with TSP. After both procedures, the postoperative outcome was uneventful and the postoperative length of hospital stay was 8 days.
Conclusions
This report confirms the feasibility of full laparoscopic TPD, and presents the first full laparoscopic pylorus- and spleen-preservation technique with conservation of the splenic vessels, without robotic assistance. No conclusions can be drawn from this report, but it shows that the laparoscopic approach provides visual magnification, improved exposure, and delicate manipulation of tissues, which may reproduce the clear advantages of laparoscopic distal pancreatectomy.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Chagasic megaesophagus (CM) as well as the presence of human papillomavirus (HPV) has been reported as etiological factors for esophageal squamous cell carcinoma (ESCC).
We assessed the prevalence of ...HPV DNA in a series of ESCCs associated or not with CM. Data obtained were further correlated to the pathological and clinical data of affected individuals.
A retrospective study was performed on 92 formalin-fixed and paraffin-embedded tissues collected from patients referred to 3 different hospitals in São Paulo, Brazil: Barretos Cancer Hospital, Barretos, São Paulo; Federal University of Triângulo Mineiro, Uberaba, Minas Gerais; and São Paulo State University, Botucatu, São Paulo. Cases were divided into 3 groups: (i) 24 patients with CM associated with ESCC (CM/ESCC); (ii) 37 patients with ESCC without CM (ESCC); and (iii) 31 patients with CM without ESCC (CM). Detection of HPV DNA was assessed in all samples by a genotyping assay combining multiplex polymerase chain reaction and bead-based Luminex technology.
We identified a high prevalence of high-risk HPV in patients in the CM group (12/31, 38.8%) and CM/ESCC (8/24, 33.3%), compared to individuals in the ESCC group (6/37, 16.3%). The individuals in the groups with cancer (ESCC and CM/ESCC) had a higher frequency of HPV-16 (4/9, 44.5% and 2/8, 25.0%). The other types of high-risk HPVs detected were HPV-31, 45, 51, 53, 56, 66, and 73. We also observed in some samples HPV coinfection by more than one viral type. Despite the high incidence of HPV, it did not show any association with the patient's clinical-pathological and molecular (TP53 mutation status) characteristics.
This is the first report of the presence of HPV DNA in CM associated with ESCC. HPV infection was more presence in megaesophagus lesions. Further studies are needed to confirm and better understand the role of persistent HPV infection in patients with CM.
Somatic mutations in the promoter region of telomerase reverse transcriptase (TERT) gene, mainly at positions c.-124 and c.-146 bp, are frequent in several human cancers; yet its presence in ...gastrointestinal stromal tumor (GIST) has not been reported to date. Herein, we searched for the presence and clinicopathological association of TERT promoter mutations in genomic DNA from 130 bona fide GISTs. We found TERT promoter mutations in 3.8% (5/130) of GISTs. The c.-124C>T mutation was the most common event, present in 2.3% (3/130), and the c.-146C>T mutation in 1.5% (2/130) of GISTs. No significant association was observed between TERT promoter mutation and patient's clinicopathological features. The present study establishes the low frequency (4%) of TERT promoter mutations in GISTs. Further studies are required to confirm our findings and to elucidate the hypothetical biological and clinical impact of TERT promoter mutation in GIST pathogenesis.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The aim of the present study was to evaluate by immunohistochemistry the prognostic meaning of the tumor marker MET (hepatocyte
growth factor) in patients submitted to surgical resection due to ...primary colorectal adenocarcinoma. Patients and Methods:
A retrospective study was carried out that included 286 consecutive patients with colorectal adenocarcinoma, submitted to
surgical resection at Barretos Cancer Hospital, from 1993 to 2002. The histopathological expression of the MET tumor marker
was evaluated using an anti-protein monoclonal antibody against MET by the streptavidin-biotin-peroxidase technique. The expression
of the tumor marker was semi-quantitative, and the slide samples were independently analyzed by three pathologists unaware
of patient clinical and histopathological data. Results: The tumor marker expression was positive in 236 (79%) out of a total
of 286 patients. This expression was statistically significantly different between stages I and IV (p=0.004), for overall
survival (p=0.009), and for cancer-related mortality rates (p=0.022). However, no association between the tumor marker and
recurrence (p=0.89) or disease-free interval (p=0.91) was observed. Conclusion: MET has shown significant expression at advanced
stages of the disease, as well as for overall survival and cancer-related mortality rates demonstrating to be a valuable marker
for poor prognosis in colorectal cancer patients.
The incidence of melanoma, one of the most aggressive of the skin cancers, has been increasing worldwide in the last few decades. Data from Latin America and Brazil remain scarce. We aimed to ...describe the demographic, clinical, and histopathological data; therapy characteristics; and survival rates of the Brazilian melanoma patient population.
We collected and analysed retrospective data from 15 years at a tertiary cancer centre. We describe patient characteristics and treatment. We calculated survival, and identified the main prognostic factors through univariate and multivariate analysis. We analysed a total of 1073 patients, with a mean age of 56.7 years. Men and women experienced similar prevalence, and 91.2% of patients had white skin. The most prevalent subtype was superficial spreading, and the most prevalent anatomic location was the trunk (32.2%), followed by the lower extremities (28%). Of all cases, 567 (52.9%) were assigned to clinical stages I and II, while 382 (32.6%) were stages III and IV. Surgery was the main treatment. Sentinel node biopsy was performed in 373 patients, with 23.8% positivity. Overall actuarial 5-year survival was 67.6%. Multivariate analysis showed that gender, serum lactate dehydrogenase (LDH) levels at diagnosis; anatomic location, TNM stage, and local recurrence were significant prognostic factors.
Overall survival was lower than worldwide rates. The main factors influencing survival were similar to those in other populations. Local recurrence was independently associated with lower survival rates. The high prevalence of advanced cases reinforces the importance of strategies to diagnose melanomas in the early stages. There is a need for future multi-institutional prospective studies to attain a better understanding of possible socioeconomic and other influences on survival among melanoma populations in Brazil and Latin America.
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