Primary Duodenal Melanoma: Challenges in Diagnosis and Management of a Rare Entity.

Primary melanoma of the duodenum is an extremely rare, aggressive and life-threatening malignant neoplasm. Published data regarding the effectiveness of current treatment strategies is limited, and our knowledge relies mostly on sporadic case reports. The diagnosis of primary duodenal melanoma is challenging and is based on the patient's medical history and findings from physical examination and radiological and endoscopic imaging as well as proper and careful pathological examinations of the tumor. Despite the many advances in cancer treatment, the prognosis for patients with this type of melanoma remains extremely poor. Delayed diagnosis at advanced disease stage, the general aggressive behavior of this neoplasm, the technical difficulty in achieving complete surgical resection, along with the rich vascular and lymphatic drainage of the intestinal mucosa, all have a negative impact on patients' outcome. In the present review, we aimed to collect and summarize the currently available data in the literature regarding the pathogenesis, clinical features, diagnosis, management and long-term outcomes of this rare, malignant tumor, in order to expand knowledge of its biological behavior and investigate optimal therapeutic options for these patients. Additionally, we present our experience of a case involving a 73-year-old female with primary duodenal melanoma, who was successfully treated with complete surgical resection.

Optimal extent of initial parathyroid resection in patients with multiple endocrine neoplasia syndrome type 1: A meta-analysis.

BACKGROUND: Hyperparathyroidism is an almost universal feature of multiple endocrine neoplasia type 1 syndrome. We present a systematic review and meta-analysis of the postoperative outcomes of patients undergoing initial operative treatment of primary hyperparathyroidism complicating multiple endocrine neoplasia 1. METHODS: A comprehensive literature search was performed with a priori defined exclusion criteria for studies comparing total parathyroidectomy, subtotal parathyroidectomy, and less than subtotal parathyroidectomy. RESULTS: Twenty-one studies incorporating 1,131 patients (272 undergoing total parathyroidectomy, 510 subtotal parathyroidectomy, and 349 less than subtotal parathyroidectomy) were identified. Pooled results revealed increased risk for long-term hypoparathyroidism in total parathyroidectomy patients (relative risk 1.61; 95% confidence interval, 1.12-2.31; P = .009) versus those undergoing subtotal parathyroidectomy. In the less than subtotal parathyroidectomy or subtotal parathyroidectomy comparison group, a greater risk for recurrence of hyperparathyroidism (relative risk 1.37; 95% confidence interval, 1.05-1.79; P = .02), persistence of hyperparathyroidism (relative risk 2.26; 95% confidence interval, 1.49-3.41; P = .0001), and reoperation for hyperparathyroidism (relative risk 2.48; 95% confidence interval, 1.65-3.73; P < .0001) was noted for less than subtotal parathyroidectomy patients, albeit with lesser risk for long-term for hypoparathyroidism (relative risk 0.47; 95% confidence interval, 0.29-0.75; P = .002). CONCLUSION: Subtotal parathyroidectomy compares favorably to total parathyroidectomy, exhibiting similar recurrence and persistence rates with a decreased propensity for long-term postoperative hypoparathyroidism. The benefit of the decreased risk of hypoparathyroidism in less than subtotal parathyroidectomy is negated by the increase in the risk for recurrence, persistence, and reoperation. Future studies evaluating the performance of less than subtotal parathyroidectomy in specific multiple endocrine neoplasia 1 phenotypes should be pursued in an effort to delineate a patient-tailored, operative approach that optimizes long-term outcomes.

The impact of preoperative sarcopenia on postoperative complications following esophagectomy for esophageal neoplasia: a systematic review and meta-analysis.

Esophageal cancer is characterized by profound changes in body composition due to dysphagia and generalized cachexia. Sarcopenia or muscle wasting is a component of cachexia associated with poor postoperative performance status. The skeletal muscle index (SMI) calculated by computed tomography scans at the level of the third lumbar vertebra is an easily quantifiable and reproducible measure of sarcopenia. The aim of this meta-analysis is to investigate the impact of preoperative sarcopenia (low SMI) on postoperative complications after esophagectomy for neoplastic lesions. In this context, a comprehensive literature search was undertaken to identify studies reporting short-term postoperative outcomes in relation to their preoperative SMI values. Cumulative risk ratios (RR) and risk differences (RD) and their respective 95% confidence intervals (CIs) were calculated using a random-effect model. A total of 11 studies incorporating 1,979 total patients (964 patients with sarcopeniaversus 1,015 without sarcopenia) were included in the final analysis. The results demonstrated a significant increase in overall morbidity (RR 1.16, 95% CI 1.01-1.33), respiratory complications (RR 1.64, 95% CI 1.21-2.22) and anastomotic leaks (RR 1.39, 95% CI 1.10-1.76) in patients with sarcopenia. No statistically significant difference was noted in overall mortality (RD 0, 95% CI -0.02-0.02) or Clavien-Dindo grade III or greater complications (RR 1.17, 95% CI 0.96-1.42). The above results demonstrate the validity of the SMI as a predictive factor for post-esophagectomy complications. Although the risk associated with sarcopenia is not prohibitive for surgery, patients with low SMI require closer vigilance during their postoperative course due to the increased propensity for respiratory and anastomotic complications.

gamma-H2AX: A potential biomarker in breast cancer.

Histone H2AX undergoes phosphorylation as an answer to DNA double-strand breaks, which in turn are part of the oncogenic procedure. The detection of gamma-H2AX can potentially serve as a biomarker for transformation of normal tissue to premalignant and consequently to malignant tissues. The aim of this study was to evaluate the clinical significance of gamma-H2AX expression in breast cancer. Gamma-H2AX expression in tissues from 110 breast cancer patients was analyzed by immunohistochemistry and correlated with clinicopathological variables. Greater tumor size, higher grade, and the number of affected lymph nodes are significantly associated with greater values of gamma-H2AX. In addition, gamma-H2AX differs significantly among patients' International Federation of Gynecology and Obstetrics stage. Higher values of estrogen receptor and progesterone receptor are significantly associated with lower gamma-H2AX values. In conclusion, a positive association between gamma-H2AX expression and infaust histopathological parameters was observed.

TYMS/KRAS/BRAF molecular profiling predicts survival following adjuvant chemotherapy in colorectal cancer.

BACKGROUND: Patients with stage II-III colorectal cancer (CRC) treated with adjuvant chemotherapy, gain a 25% survival benefit. In the context of personalized medicine, there is a need to identify patients with CRC who may benefit from adjuvant chemotherapy. Molecular profiling could guide treatment decisions in these patients. Thymidylate synthase (TYMS) gene polymorphisms, KRAS and BRAF could be included in the molecular profile under consideration. AIM: To investigate the association of TYMS gene polymorphisms, KRAS and BRAF mutations with survival of CRC patients treated with chemotherapy. METHODS: A retrospective study studied formalin-fixed paraffin-embedded tissues (FFPEs) of consecutive patients treated with adjuvant chemotherapy during January/2005-January/2007. FFPEs were analysed with PCR for the detection of TYMS polymorphisms, mutated KRAS (mKRAS) and BRAF (mBRAF). Patients were classified into three groups (high, medium and low risk) according to 5'UTR TYMS polymorphisms Similarly, based on 3'UTR polymorphism ins/loss of heterozygosity (LOH) patients were allocated into two groups (high and low risk of relapse, respectively). Cox regression models examined the associated 5-year survival outcomes. RESULTS: One hundred and thirty patients with early stage CRC (stage I-II: 55 patients; stage III 75 patients; colon: 70 patients; rectal: 60 patients) were treated with surgery and chemotherapy. The 5-year disease free survival and overall survival rate was 61.6% and 73.9% respectively. 5'UTR polymorphisms of intermediate TYMS polymorphisms (2RG/3RG, 2RG/LOH, 3RC/LOH) were associated with lower risk for relapse [hazard ratio (HR) 0.320, P = 0.02 and HR 0.343, P = 0.013 respectively] and death (HR 0.368, P = 0.031 and HR 0.394, P = 0.029 respectively). The 3'UTR polymorphism ins/LOH was independently associated with increased risk for disease recurrence (P = 0.001) and death (P = 0.005). mBRAF (3.8% of patients) was associated with increased risk of death (HR 4.500, P = 0.022) whereas mKRAS (39% of patients) not. CONCLUSION: Prospective validating studies are required to confirm whether 2RG/3RG, 2RG/LOH, 3RC/LOH, absence of ins/LOH and wild type BRAF may indicate patients at lower risk of relapse following adjuvant chemotherapy.

A huge asymptomatic pheochromocytoma.

Due to their evolution in the retroperitoneal space, pheochromocytomas may grow significantly in size and remain asymptomatic for a long period of time. Normal values of urine catecholamine levels must not preclude the diagnosis of these endocrine lesions.

Integrating TYMS, KRAS and BRAF testing in patients with metastatic colorectal cancer.

AIM: To investigate the impact of thymidylate synthase (TYMS), KRAS and BRAF in the survival of metastatic colorectal cancer (mCRC) patients treated with chemotherapy. METHODS: Clinical data were collected retrospectively from records of consecutive patients with mCRC treated with fluoropyrimidine-based chemotherapy from 1/2005 to 1/2007. Formalin-fixed paraffin-embedded tissues were retrieved for analysis. TYMS genotypes were identified with restriction fragment analysis PCR, while KRAS and BRAF mutation status was evaluated using real-time PCR assays. TYMS gene polymorphisms of each of the 3' untranslated region (UTR) and 5'UTR were classified into three groups according to the probability they have for high, medium and low TYMS expression (and similar levels of risk) based on evidence from previous studies. Univariate and multivariate survival analyses were performed. RESULTS: The analysis recovered 89 patients with mCRC (46.1% de novo metastatic disease and 53.9% relapsed). Of these, 46 patients (51.7%) had colon cancer and 43 (48.3%) rectal cancer as primary. All patients were treated with fluoropyrimidine-based chemotherapy (5FU or capecitabine) as single-agent or in combination with irinotecan or/and oxaliplatin or/and bevacizumab. With a median follow-up time of 14.8 mo (range 0-119.8), 85 patients (95.5%) experienced disease progression, and 63 deaths (70.8%) were recorded. The 3-year and 5-year OS rate was 25.4% and 7.7% while the 3-year progression-free survival rate was 7.1%. Multivariate analysis of TYMS polymorphisms, KRAS and BRAF with clinicopathological parameters indicated that TYMS 3'UTR polymorphisms are associated with risk for disease progression and death (P < 0.05 and P < 0.03 respectively). When compared to tumors without any del allele (genotypes ins/ins and ins/loss of heterozygosity (LOH) linked with high TYMS expression) tumors with del/del genotype (low expression group) and tumors with ins/del or del/LOH (intermediate expression group) have lower risk for disease progression (HR = 0.432, 95%CI: 0.198-0.946, P < 0.04 and HR = 0.513, 95%CI: 0.287-0.919, P < 0.03 respectively) and death (HR = 0.366, 95%CI: 0.162-0.827, P < 0.02 and HR = 0.559, 95%CI: 0.309-1.113, P < 0.06 respectively). Additionally, KRAS mutation was associated independently with the risk of disease progression (HR = 1.600, 95%CI: 1.011-2.531, P < 0.05). The addition of irinotecan in 1st line chemotherapy was associated independently with lower risk for disease progression and death (HR = 0.600, 95%CI: 0.372-0.969, P < 0.04 and HR = 0.352, 95%CI: 0.164-0.757, P < 0.01 respectively). CONCLUSION: The TYMS genotypes ins/ins and ins/LOH associate with worst prognosis in mCRC patients under fluoropyrimidine-based chemotherapy. Large prospective studies are needed for validation of our findings.

A giant squamous cell carcinoma of the skin of the thoracic wall: a case report and review of the literature.

BACKGROUND: We report a case of a 48-year-old white woman who presented with a huge cutaneous protruding tumor of the thoracic wall below her left breast. CASE PRESENTATION: The lesion was excised with clear margins from the adjacent skin, and subcutaneous tissue was left to heal with second intention. A histological examination of the surgical specimen revealed a well-differentiated infiltrative cutaneous squamous cell carcinoma. Our patient neglected to attend our Oncological Department to receive chemotherapy. Today, 12 months after surgery, she is alive and without evidence of disease recurrence. CONCLUSIONS: Cutaneous squamous cell carcinoma can reach a huge size if left untreated. Surgery is the primary mode of treatment, followed by chemotherapy if applicable.

gamma-H2AX: Can it be established as a classical cancer prognostic factor?

Double-strand breaks are among the first procedures taking place in cancer formation and progression as a result of endogenic and exogenic factors. The histone variant H2AX undergoes phosphorylation at serine 139 due to double-strand breaks, and the gamma-H2AX is formatted as a result of genomic instability. The detection of gamma-H2AX can potentially serve as a biomarker for transformation of normal tissue to premalignant and consequently to malignant tissues. gamma-H2AX has already been investigated in a variety of cancer types, including breast, lung, colon, cervix, and ovary cancers. The prognostic value of gamma-H2AX is indicated in certain cancer types, such as breast or endometrial cancer, but further investigation is needed to establish gamma-H2AX as a prognostic marker. This review outlines the role of gamma-H2AX in cell cycle, and its formation as a result of DNA damage. We investigate the role of gamma-H2AX formation in several cancer types and its correlation with other prognostic factors, and we try to find out whether it fulfills the requirements for its establishment as a classical cancer prognostic factor.

Early Diagnosis and Surgical Treatment for Necrotizing Fasciitis: A Multicenter Study.

BACKGROUND: Necrotizing fasciitis (NF) is a group of relatively rare infections, usually caused by two or more pathogens. It affects the skin and subcutaneous tissues of lower and upper limbs, perineal area (Fournier's gangrene), and the abdominal wall. Early diagnosis and aggressive surgical management are of high significance for the management of this potentially lethal disease. METHODS: We conducted a retrospective study in patients who presented, during the last decade, at four University Surgical Departments in the area of Athens, Greece, with an admission diagnosis of NF. Demographic, clinical, and laboratory data were gathered, and the preoperative and surgical treatment, as well as the postoperative treatment was analyzed for these patients. RESULTS: A total of 62 patients were included in the study. The mean age of patients was 63.7 (47 male patients). Advanced age (over 65 years) (P < 0.01) and female sex (P = 0.04) correlated significantly with mortality. Perineum was the mostly infected site (46.8%), followed by the lower limbs (35.5%), the upper limbs, and the axillary region (8.1%). Diabetes mellitus was the most common coexisting disease (40.3%), followed by hypertension (25.8%) and obesity (17.7%). The most common symptom was local pain and tenderness (90.3%). Septic shock occurred in eight patients (12.9%) and strongly correlated with mortality (P < 0.01). Laboratory data were used to calculate the LRINEC score of every patient retrospectively; 26 patients (41.9%) had LRINEC score under 6, 20 patients (32.3%) had LRINEC score 6-8, and 16 patients (25.8%) had LRINEC score >9. Surgical debridement was performed in all patients (mean number of repeated debridement 4.8), and in 16 cases (25.8%) the infected limb was amputated. The mean length of hospital stay was 19.7 days, and the overall mortality rate of our series was 17.7%. CONCLUSION: Diagnosis of NF requires high suspect among clinicians, as its clinical image is non-specific. Laboratory tests can depict the severity of the disease; therefore, they must be carefully evaluated. Urgent surgical debridement is the mainstay of treatment in all patients; the need of repetitive surgical debridement is undisputed.

Idiopathic Double Perforation of the Gastrointestinal Tract.

A 73-year old woman was operated on with diffuse peritonitis and multiple abscesses throughout the mesentery which were drained. After the operation the patient could not recover. After an indicative computerized tomography the patient was re-explored. Perforation of the ileum and gastric perforation at the pylorus were found. There was no history of underline disease. The double perforation of the GI tract was surgically managed but the patient's course was fatal.

Current Trends in Laparoscopic Ventral Hernia Repair.

BACKGROUND AND OBJECTIVES: The purpose of this study was to analyze the surgical technique, postoperative complications, and possible recurrence after laparoscopic ventral hernia repair (LVHR) in comparison with open ventral hernia repair (OVHR), based on the international literature. DATABASE: A Medline search of the current English literature was performed using the terms laparoscopic ventral hernia repair and incisional hernia repair. CONCLUSIONS: LVHR is a safe alternative to the open method, with the main advantages being minimal postoperative pain, shorter recovery, and decreased wound and mesh infections. Incidental enterotomy can be avoided by using a meticulous technique and sharp dissection to avoid thermal injury.

Epidermoid cyst of an intrapancreatic accessory spleen: a case report and literature review.

BACKGROUND: An epidermoid cyst in an intrapancreatic accessory spleen is a rare lesion. Despite advances in radiologic techniques, in most cases it has been diagnosed preoperatively as a possible pancreatic neoplasm. CASE PRESENTATION: Herein, we present a 63-year-old Caucasian woman, diagnosed preoperatively with enhanced-contrast abdominal computed tomography, as having a potential cystic tumor in the tail of the pancreas. The patient underwent a distal pancreatectomy and splenectomy, and the histological examination revealed the presence of an epidermoid cyst of an accessory intrapancreatic spleen. CONCLUSIONS: Familiarity with the imaging features, the clinical presentation and the location of the cyst are important to consider if this rare entity is to be included in the differential diagnosis of cystic neoplasms of the pancreas.

Current concepts in the management of necrotizing fasciitis.

Necrotizing fasciitis (NF) is a severe, rare, potentially lethal soft tissue infection that develops in the scrotum and perineum, the abdominal wall, or the extremities. The infection progresses rapidly, and septic shock may ensue; hence, the mortality rate is high (median mortality 32.2%). Prognosis becomes poorer in the presence of co-morbidities, such as diabetes mellitus, immunosuppression, chronic alcohol disease, chronic renal failure, and liver cirrhosis. NF is classified into four types, depending on microbiological findings. Most cases are polymicrobial, classed as type I. The clinical status of the patient varies from erythema, swelling, and tenderness in the early stage to skin ischemia with blisters and bullae in the advanced stage of infection. In its fulminant form, the patient is critically ill with signs and symptoms of severe septic shock and multiple organ dysfunction. The clinical condition is the most important clue for diagnosis. However, in equivocal cases, the diagnosis and severity of the infection can be secured with laboratory-based scoring systems, such as the laboratory risk indicator for necrotizing fasciitis score or Fournier's gangrene severity index score, especially in regard to Fournier's gangrene. Computed tomography or ultrasonography can be helpful, but definitive diagnosis is attained by exploratory surgery at the infected sites. Management of the infection begins with broad-spectrum antibiotics, but early and aggressive drainage and meticulous debridement constitute the mainstay of treatment. Postoperative management of the surgical wound is also important for the patient's survival, along with proper nutrition. The vacuum-assisted closure system has proved to be helpful in wound management, with its combined benefits of continuous cleansing of the wound and the formation of granulation tissue.

Potential benefits of pro- and prebiotics on intestinal mucosal immunity and intestinal barrier in short bowel syndrome.

The mechanism of impaired gut barrier function in patients with short bowel syndrome (SBS) is poorly understood and includes decreased intestinal motility leading to bacterial overgrowth, a reduction in gut-associated lymphoid tissue following the loss of intestinal length, inhibition of mucosal immunity of the small intestine by intravenous total parental nutrition, and changes in intestinal permeability to macromolecules. Novel therapeutic strategies (i.e. nutritive and surgical) have been introduced in order to prevent the establishment or improve the outcome of this prevalent disease. Pre- and probiotics as a nutritive supplement are already known to be very active in the intestinal tract (mainly in the colon) by maintaining a healthy gut microflora and influencing metabolic, trophic and protective mechanisms, such as the production of SCFA which influence epithelial cell metabolism, turnover and apoptosis. Probiotics have been recommended for patients suffering from SBS in order to decrease bacterial overgrowth and prevent bacterial translocation, two major mechanisms in the pathogenesis of SBS. The present review discusses the research available in the international literature, clinical and experimental, regarding probiotic supplementation for this complicated group of patients based on the clinical spectrum and pathophysiological aspects of the syndrome. The clinical data that were collected for the purposes of the present review suggest that it is difficult to correctly characterise probiotics as a preventive or therapeutic measure. It is very challenging after all to examine the relationship of the bacterial flora, the intestinal barrier and the probiotics as, according to the latest knowledge, demonstrate an interesting interaction.

Embolization as an alternative treatment of insulinoma in a patient with multiple endocrine neoplasia type 1 syndrome.

Insulinoma is a rare neuroendocrine tumor, most commonly originating from the pancreas, which is either sporadic or familial as a component of multiple endocrine neoplasia type 1 syndrome (MEN1). It is characterized by increased insulin secretion leading to hypoglycemia. Surgical removal is considered the treatment of choice, with limited side effects and relatively low morbidity and mortality, both being improved by the laparoscopic procedure. We present the case of a 30-year-old patient with MEN1 and recurrent insulinoma with severe hypoglycemic episodes who could not be surgically treated due to the adherence of the tumor to large blood vessels and to prior multiple surgical operations. He was treated by repeated embolization using spherical polyvinyl alcohol particles, resulting in shrinkage of the tumor, improvement of the frequency and severity of the hypoglycemic episodes, and better quality of life.

Gastroesophageal reflux disease: medical or surgical treatment?

BACKGROUND: Gastroesophageal reflux disease is a common condition with increasing prevalence worldwide. The disease encompasses a broad spectrum of clinical symptoms and disorders from simple heartburn without esophagitis to erosive esophagitis with severe complications, such as esophageal strictures and intestinal metaplasia. Diagnosis is based mainly on ambulatory esophageal pH testing and endoscopy. There has been a long-standing debate about the best treatment approach for this troublesome disease. METHODS AND RESULTS: Medical treatment with PPIs has an excellent efficacy in reversing the symptoms of GERD, but they should be taken for life, and long-term side effects do exist. However, patients who desire a permanent cure and have severe complications or cannot tolerate long-term treatment with PPIs are candidates for surgical treatment. Laparoscopic antireflux surgery achieves a significant symptom control, increased patient satisfaction, and complete withdrawal of antireflux medications, in the majority of patients. CONCLUSION: Surgical treatment should be reserved mainly for young patients seeking permanent results. However, the choice of the treatment schedule should be individualized for every patient. It is up to the patient, the physician and the surgeon to decide the best treatment option for individual cases.

Laparoscopic ventral hernia repair: pros and cons compared with open hernia repair.

BACKGROUND: The purpose of this study was to analyse the surgical techniques, perioperative complications, and recurrence rate of laparoscopic ventral hernia repair (LVHR), in comparison with the open ventral hernia repair (OVHR), based on the international literature. METHODS: A Medline search of the English literature was performed using the term "laparoscopic ventral hernia repair." Further articles were found by cross-referencing the references of each main article. RESULTS: Current literature on the topic suggests that LVHR is a safe alternative to the open method with the main advantages being minimal postoperative pain, a shorter convalescence period, and better cosmetic results. Main complications after the laparoscopic approach, such as incidental enterotomy, protracted pain, postoperative seroma, or mesh infection occur at an acceptable rate. Furthermore, most articles favor LVHR versus OVHR in terms of recurrence rate. CONCLUSIONS: Although further randomized studies are needed to draw safe conclusions in terms of complications and recurrence, LVHR is fast becoming the standard approach in the repair of abdominal wall hernias.