Frequency of Human Papillomavirus Detection in Chagasic Megaesophagus Associated or Not with Esophageal Squamous Cell Carcinoma.

BACKGROUND: Chagasic megaesophagus (CM) as well as the presence of human papillomavirus (HPV) has been reported as etiological factors for esophageal squamous cell carcinoma (ESCC). OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Co-expression of monocarboxylate transporter 1 (MCT1) and its chaperone (CD147) is associated with low survival in patients with gastrointestinal stromal tumors (GISTs).

Monocarboxylate transporters (MCTs) have been described to play an important role in cancer, but to date there are no reports on the significance of MCT expression in gastrointestinal stromal tumors (GISTs). The aim of the present work was to assess the value of MCT expression, as well as co-expression with the MCT chaperone CD147 in GISTs and evaluate their clinical-pathological significance. We analyzed the immunohistochemical expression of MCT1, MCT2, MCT4 and CD147 in a series of 64 GISTs molecularly characterized for KIT, PDGFRA and BRAF mutations. MCT1, MCT2 and MCT4 were highly expressed in GISTs. CD147 expression was associated with mutated KIT (p = 0.039), as well as a progressive increase in Fletcher's Risk of Malignancy (p = 0.020). Importantly, co-expression of MCT1 with CD147 was associated with low patient's overall survival (p = 0.037). These findings suggest that co-expression of MCT1 with its chaperone CD147 is involved in GISTs aggressiveness, pointing to a contribution of cancer cell metabolic adaptations in GIST development and/or progression.

EARLY ORAL FEEDING POST-UPPER GASTROINTESTINAL TRACT RESECTION AND PRIMARY ANASTOMOSIS IN ONCOLOGY.

BACKGROUND: The practice of starving patients in the immediate period after upper gastrointestinal surgery is widespread. Early oral intake has been shown to be feasible and may result in faster recovery and decrease length of hospital. AIM: To evaluate the feasibility and safety of oral nutrition on postoperative early feeding after upper gastrointestinal surgeries. METHODS: Observational cohort design study with convenience retrospective data in both genders, over 18 years, undergoing to total gastrectomy and/or elective esophagectomy. They have received oral or enteral nutrition in less than 48 h after surgery, and among those who started with enteral nutrition, the oral feeding up to seven days. RESULTS: The study was performed in 161 patients, 24 (14.9%) submitted to esophagectomy, 132 (82%) to total gastrectomy and five (3.1%) to esophagogastrectomy. Was observed good dietary acceptance and low percentage (29%) of gastrointestinal intolerances, more pronounced among those with enteral diet. Most of the patients did not present postoperative complications, 11 (6.8%) were reopened, five (3.1%) had fistulas, three (1.9%) wound dehiscence, three (1.9%) fistula more wound dehiscence and six (3.7%) other non-infectious complications. CONCLUSION: Early oral diet is safe and viable for patients undergoing upper gastrointestinal surgery.

PIK3CA mutations are frequent in esophageal squamous cell carcinoma associated with chagasic megaesophagus and are associated with a worse patient outcome.

BACKGROUND: 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. OBJECTIVE: We analyzed hotspot PIK3CA 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 PIK3CA mutations with patients' clinical and pathological features. METHODS: 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). PIK3CA hotspot mutations in exons 9 and 20 were evaluated by PCR followed by direct sequencing technique. RESULTS: PIK3CA 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, PIK3CA 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 PIK3CA mutations and patients' clinical features or TP53 mutation profile. CONCLUSION: This is the first report on the presence of PIK3CA mutations in esophageal cancer associated with chagasic megaesophagus. The detection of PIK3CA 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.

Presence of microsatellite instability in esophageal squamous cell carcinoma associated with chagasic megaesophagus.

AIM: The molecular pathogenesis of esophageal squamous cell carcinoma (ESCC) has been increasingly studied, but there is no report on the role of MSI in ESCC development associated with chagasic megaesophagus (CM).Results/methodology: In four ESCC/CM (4/19) we found microsatellite instability (MSI) alterations (21.1%), being three MSI-L (15.8%) and one MSI-H (5.3%). Four out of 35 ESCC cases showed MSI-L (11.4%) and only one out of 26 CM cases presented MSI-L (3.9%). The MSI-H was observed in an ESCC/CM patient that presents lack of MSH6 immunostaining corroborating deficiency in MMR pathway. Interestingly, the MSI-H ESCC/CM case also presented a deletion the HSP110 poly(T)17 gene. DISCUSSION/CONCLUSION: Taking together, we concluded that MSI is a rare event in esophageal squamous cell carcinoma, but can be associated with CM.

Comparison of laparoscopic total gastrectomy and laparotomic total gastrectomy for gastric cancer.

BACKGROUND: 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. AIM: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

Melanoma characteristics in Brazil: demographics, treatment, and survival analysis.

BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.

Full laparoscopic total pancreatectomy with and without spleen and pylorus preservation: a feasibility report.

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.

[Boerhaave's syndrome: case report]. / Síndrome de Boerhaave: relato de caso.

Spontaneous esophageal rupture carries high morbidity and mortality. The main prognostic factor is early diagnosis, before 12 hours, and appropriate treatment. This is a case report of a 41-years-old man with late esophageal rupture diagnosis treated successfully with transmediatinal esophagectomy and esophageal-gastric tube cervical anastomosis.

Bypass laparoscopic procedure for palliation of esophageal cancer.

Esophageal cancer is a devastating disease with rapidly increasing incidence in Western countries. Dysphagia is the most common complication, causing severe malnutrition and reduced quality of life. A 69-year-old male with persistent esophageal cancer after radiation therapy was subjected to palliative by-pass surgery using a laparoscopic approach. Due to the advanced stage at diagnosis, palliative treatment was a more realistic option. Dysphagia is a most distressing symptom of this disease, causing malnutrition and reducing quality of life. The goal of palliation is to improve swallowing. The most common methods applied are endoscopic stenting, radiation therapy (external or brachytherapy), chemotherapy, yttrium-aluminum-garnet laser rechanneling or endoscopic dilatation. Palliative surgery is rarely proposed due to morbidity and complications. This paper demonstrates an update in the technique proposed by Postlethwait in 1979 for palliation of esophageal cancer.

Early oral feeding post-upper gastrointestinal tract resection and primary anastomosis in oncology / Realimentação oral precoce após ressecções e anastomose primária do trato gastrointestinal alto em oncologia

ABSTRACT Background: The practice of starving patients in the immediate period after upper gastrointestinal surgery is widespread. Early oral intake has been shown to be feasible and may result in faster recovery and decrease length of hospital. Aim: To evaluate the feasibility and safety of oral nutrition on postoperative early feeding after upper gastrointestinal surgeries. Methods: Observational cohort design study with convenience retrospective data in both genders, over 18 years, undergoing to total gastrectomy and/or elective esophagectomy. They have received oral or enteral nutrition in less than 48 h after surgery, and among those who started with enteral nutrition, the oral feeding up to seven days. Results: The study was performed in 161 patients, 24 (14.9%) submitted to esophagectomy, 132 (82%) to total gastrectomy and five (3.1%) to esophagogastrectomy. Was observed good dietary acceptance and low percentage (29%) of gastrointestinal intolerances, more pronounced among those with enteral diet. Most of the patients did not present postoperative complications, 11 (6.8%) were reopened, five (3.1%) had fistulas, three (1.9%) wound dehiscence, three (1.9%) fistula more wound dehiscence and six (3.7%) other non-infectious complications. Conclusion: Early oral diet is safe and viable for patients undergoing upper gastrointestinal surgery.

RESUMO Racional: Os níveis do antígeno carcinoembriônico no lavado peritoneal têm sido demonstrados como possível fator prognóstico de recidiva e mortalidade em pacientes com câncer gástrico. Objetivos: Medir seus níveis em lavado peritoneal durante operação de ressecção de câncer gástrico e ver se eles aumentados estão relacionados com mortalidade, recorrência, recidiva e outros fatores prognósticos. Métodos: Foi realizado lavado peritoneal durante ressecções de câncer gástrico; os níveis do antígeno carcinoembriônico nesse lavado maiores ou iguais a 210 ng/g foram considerados aumentados ou positivos. Resultados: Foram estudados 30 pacientes, destes, 33,33 % apresentaram níveis aumentados, os quais foram fator de risco para mortalidade em seis meses OR: 8,5 (1,458-49,539) IC 95%, mortalidade geral RR: 2,111 (1,314-3,391) IC 95%, mortalidade devido à doença OR: 12 (1,885-76,376) IC 95%, recorrência peritoneal OR: 9 (1,325-61,138) IC 95%, e recidiva ou progressão da doença OR: 27 (2,705-269,460) IC 95%. Conclusões: Os níveis aumentados do antígeno carcinoembriônico no lavado peritoneal foram fatores de risco para mortalidade, recorrência peritoneal, recidiva e progressão da doença em pacientes com câncer gástrico.

Prognostic and risk factors in patients with locally advanced cutaneous squamous cell carcinoma of the trunk and extremities.

55 patients with advanced cutaneous squamous cell carcinoma (CSCC) of the trunk and extremities were studied. A Tissue Microarray was constructed using immunohistochemistry to quantify expression of the HER family, E-cadherins, and podoplanin. Clinical and histopathological factors related to lymph node metastasis and prognosis were also established. Primary tumor positivity was 25.5% for EGFR, 87.3% for HER-3, and 48.1% for HER-4. Metastases were positive for EGFR in 41.7%, for HER-3 in 83.3%, and HER-4 in 43.5%. HER-2 was negative in all samples. Membrane E-cadherin and cytoplasmic E-cadherin were positive in 47.3% and 30.2% of primary tumors and 45.5% and 27.3% of metastases, respectively. Podoplanin was positive in 41.8% of primary tumors and 41.7% of metastases. Intratumoral lymphocytic infiltrate was associated with lymph node metastasis. Patients with T3 tumors had better cancer-specific survival (CSS) than those with T4 tumors; patients with no lymph node involvement had better CSS than patients with N1 tumors. Undifferentiated tumors and hyperexpression of podoplanin were negative prognostic indicators on multivariate analysis.

Lymphangiogenic VEGF-C and VEGFR-3 expression in genetically characterised gastrointestinal stromal tumours.

This study aimed to assess the distribution of VEGF-C and VEGFR-3 expression in gastrointestinal stromal tumours (GISTs), and to analyse the value of lymphatic vessel density (LVD) in a tumour that is believed to preferentially metastasize through blood vessel conduits. A panel of immunohistochemical antibodies was used to evaluate 51 cases of genetically characterised GISTs: VEGF-C, VEGFR-3, D2-40 (for LVD assessment) and CD31 (for blood vessel density--BDV--assessment). The results were correlated with the clinical-pathological data. The large majority of cases (86.2%; 44/51) showed a mutation of the KIT gene, most of them (72.5%; 37/51) revealing mutations in exon 11. VEGFR-3 was predominantly expressed in KIT mutated GISTs (p=0.019). High LVD was correlated with the absence of metastasis (p=0.010) and high BVD showed a positive correlation with the occurrence of metastasis (p=0.049). The strong expression of VEGF-C and VEGFR-3 in GIST's cells was not correlated with the clinical parameters of aggressiveness, nor with high LVD.

MET Is highly expressed in advanced stages of colorectal cancer and indicates worse prognosis and mortality.

UNLABELLED: 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.