Probing the O-glycoproteome of gastric cancer cell lines for biomarker discovery.

Circulating O-glycoproteins shed from cancer cells represent important serum biomarkers for diagnostic and prognostic purposes. We have recently shown that selective detection of cancer-associated aberrant glycoforms of circulating O-glycoprotein biomarkers can increase specificity of cancer biomarker assays. However, the current knowledge of secreted and circulating O-glycoproteins is limited. Here, we used the COSMC KO "SimpleCell" (SC) strategy to characterize the O-glycoproteome of two gastric cancer SimpleCell lines (AGS, MKN45) as well as a gastric cell line (KATO III) which naturally expresses at least partially truncated O-glycans. Overall, we identified 499 O-glycoproteins and 1236 O-glycosites in gastric cancer SimpleCells, and a total 47 O-glycoproteins and 73 O-glycosites in the KATO III cell line. We next modified the glycoproteomic strategy to apply it to pools of sera from gastric cancer and healthy individuals to identify circulating O-glycoproteins with the STn glycoform. We identified 37 O-glycoproteins in the pool of cancer sera, and only nine of these were also found in sera from healthy individuals. Two identified candidate O-glycoprotein biomarkers (CD44 and GalNAc-T5) circulating with the STn glycoform were further validated as being expressed in gastric cancer tissue. A proximity ligation assay was used to show that CD44 was expressed with the STn glycoform in gastric cancer tissues. The study provides a discovery strategy for aberrantly glycosylated O-glycoproteins and a set of O-glycoprotein candidates with biomarker potential in gastric cancer.

Validation study of the European Portuguese version of the Confusion Assessment Method (CAM).

BACKGROUND: The Confusion Assessment Method (CAM) is the most widely used delirium screening instrument. The aim of this study was to evaluate the reliability and validity of the European Portuguese version of CAM. METHODS: The sample included elderly patients (≥65 years), admitted for at least 48 h, into two intermediate care units (ICMU) of Intensive Medicine and Surgical Services in a university hospital. Exclusion criteria were: score ≤11 on the Glasgow Coma Scale (GCS), blindness/deafness, inability to communicate and to speak Portuguese. For concurrent validity, a blinded assessment was conducted by a psychiatrist (DSM-IV-TR, as a reference standard) and by a trained researcher (CAM). This instrument was also compared with other cognitive measures to evaluate convergent validity. Inter-rater reliability was also assessed. RESULTS: In this sample (n = 208), 25% (n = 53) of the patients had delirium, according to DSM-IV-TR. Using this reference standard, the CAM had a moderate sensitivity of 79% and an excellent specificity of 99%. The positive predictive value was 95%, indicating a strong ability to confirm delirium with a positive test result, and the negative predictive value was lower (93%). Good convergent validity was also found, in particular with Mini-Mental State Examination (MMSE) (rs = -0.676; p ≤0.01) and Digit Span Test (DST) forward (rs = -0.605; p ≤0.01), as well as a high inter-rater reliability (diagnostic k = 1.00; single items' k between 0.65 and 1.00). CONCLUSION: Robust results on concurrent and convergent validity and good reliability were achieved. This version was shown to be a valid and reliable instrument for delirium detection in elderly patients hospitalized in intermediate care units.

Immunohistochemical molecular phenotypes of gastric cancer based on SOX2 and CDX2 predict patient outcome.

BACKGROUND: Gastric cancer remains a serious health concern worldwide. Patients would greatly benefit from the discovery of new biomarkers that predict outcome more accurately and allow better treatment and follow-up decisions. Here, we used a retrospective, observational study to assess the expression and prognostic value of the transcription factors SOX2 and CDX2 in gastric cancer. METHODS: SOX2, CDX2, MUC5AC and MUC2 expression were assessed in 201 gastric tumors by immunohistochemistry. SOX2 and CDX2 expression were crossed with clinicopathological and follow-up data to determine their impact on tumor behavior and outcome. Moreover, SOX2 locus copy number status was assessed by FISH (N = 21) and Copy Number Variation Assay (N = 62). RESULTS: SOX2 was expressed in 52% of the gastric tumors and was significantly associated with male gender, T stage and N stage. Moreover, SOX2 expression predicted poorer patient survival, and the combination with CDX2 defined two molecular phenotypes, SOX2+CDX2- versus SOX2-CDX2+, that predict the worst and the best long-term patients' outcome. These profiles combined with clinicopathological parameters stratify the prognosis of patients with intestinal and expanding tumors and in those without signs of venous invasion. Finally, SOX2 locus copy number gains were found in 93% of the samples reaching the amplification threshold in 14% and significantly associating with protein expression. CONCLUSIONS: We showed, for the first time, that SOX2 combined with CDX2 expression profile in gastric cancer segregate patients into different prognostic groups, complementing the clinicopathological information. We further demonstrate a molecular mechanism for SOX2 expression in a subset of gastric cancer cases.

Pilot study on the European Portuguese version of the Confusion Assessment Method.

OBJECTIVE: To present the pilot study on the European Portuguese validation of the Confusion Assessment Method (CAM). METHODS: The translation process was carried out according to International Society Pharmacoeconomics and Outcomes Research guidelines with trained researchers and inter-rater reliability assessment. The study included 50 elderly patients, admitted (≥24 h) to two intermediate care units. Exclusion criteria were: Glasgow Coma Scale (total score ≤11), blindness/deafness, inability to communicate and not able to speak Portuguese. The sensitivity and specificity of CAM were assessed, with DSM-IV-TR criteria of delirium used as a reference standard. RESULTS: Findings revealed excellent inter-rater reliability (k>0.81), moderate sensitivity (73%) and excellent specificity (95%). CONCLUSION: These preliminary results suggested that this version emerges as a promising diagnostic instrument for delirium.

Routine Use of Neck Drains Following Thyroid Operations to Prevent Complications Is No Longer Advisable.

BACKGROUND: The use of cervical drains to prevent cervical hematoma or seroma after thyroidectomy remains a controversial issue. OBJECTIVE: Identify clinical and surgical risk factors for hematoma or seroma and evaluate the usefulness of routine use of drains following thyroid surgery. MATERIAL AND METHODS: The authors conducted a retrospective multicentric study related to consecutive patients submitted to thyroid surgery in seven Portuguese hospitals between January 2018 and December 2020 (n=945). The data collected included the following parameters: age and gender of the patients, anticoagulation or anti-aggregating therapy, histological diagnoses, type of surgery, the presence or absence of postoperative drains, thyroid weight, length of hospital stay, postoperative complications, and reinterventions. In this study, surgical complications evaluated were limited to the presence of hematoma or seroma. A total of 945 patients who underwent thyroid surgery were included in the study. Twenty-seven patients (2.9%, n=27) experienced complications classified as hematomas or seromas. In the series, significant differences were observed between the two groups according to hypocoagulation or anti-aggregation status (OR=3.62; 95% CI 1.14-11.4) (p=0.001) and the nature of histological diagnosis (toxic vs. non-toxic benign disease) (OR=6.59; 95% CI 1.83-23.7). Hypocoagulation or anti-aggregation status were independently associated with a higher risk of complications. The presence of drains was associated with longer hospitalization periods (p<0.001) and not a decreased need for reintervention. CONCLUSION: Cervical hematoma or seroma are rare complications associated with both hypocoagulation and anti-aggregation therapy and with the presence of benign toxic pathology. The use of drains does not decrease the need for reintervention and is even associated with a longer length of hospital stay; therefore, their routine use should not be advised.

Unveiling a Small Bowel Obstruction: A Case of a Neuroendocrine Ileal Tumor.

Neuroendocrine tumors (NETs) are rare, slow-growing tumors originating from the diffuse neuroendocrine cell system, predominantly affecting the digestive tract. Small bowel neuroendocrine tumors (SBNETs) may present with nonspecific symptoms, such as abdominal pain, or with intermittent intestinal obstruction. This case outlines the diagnostic journey of a septuagenarian male with prolonged abdominal symptoms and weight loss. Despite extensive investigation, a definitive cause remained elusive. Recurrent partial intestinal obstruction led to surgical exploration and segmental resection. Pathology confirmed a NET. The case underscores the importance of considering intestinal neoplasia in older patients with recurrent partial small bowel obstruction.

Synchronous Gastric and Rectal Adenocarcinoma With Complete Response After Total Neoadjuvant Therapy: A Case Report.

Synchronous gastric cancer with another neoplasm is a rare condition, with colorectal cancer being the most frequently associated neoplasm. This article presents a case of a 76-year-old male diagnosed with synchronous gastric and rectal cancer with complete remission of gastric and rectal neoplasms after adjuvant therapy. The patient exhibited symptoms prompting upper and lower endoscopies, revealing gastric and rectal adenocarcinomas, respectively. Staging was performed, and due to the locally advanced nature of both malignancies, the patient underwent total neoadjuvant therapy (TNT) for rectal cancer. The treatment consisted of external radiotherapy and neoadjuvant chemotherapy with oxaliplatin, leucovorin, folinic acid, and fluorouracil (FOLFOX). Remarkably, after seven cycles, a complete clinical response of the rectal neoplasm was achieved. Subsequent surgical resection included simultaneous subtotal gastrectomy and rectal anterior resection, resulting in a complete pathological response for both tumors. To the best of our knowledge, it is among the first cases to report a full pathological response in gastric cancer following TNT intended for rectal cancer.

An Unusual Coexistence: Right-Sided Colon Cancer and Intestinal Malrotation in an Adult.

Intestinal malrotation (IM), a rare congenital anomaly disrupting typical embryonic rotation around the superior mesenteric artery, is exceptionally uncommon in adults, with its link to colon cancer being even rarer. This article presents a case of colonic cancer in conjunction with IM in a 63-year-old male. Image studies and intraoperative findings show signs of IM. Open resection was performed due to concerns about vascular anomalies and abnormal lymphatic drainage. The case underscores the rarity of colon cancer in a malrotated gut, highlighting the necessity of preoperative identification for precise surgical planning and emphasizing the importance of careful dissection to prevent inadvertent vascular injury.

Appendiceal Neoplasm: It's Never What It Seems.

Appendiceal neoplasms are a rare and heterogeneous condition with a non-specific clinical presentation, often concealing intricate predicaments; hence they require complex and diverse management. The present case report aims not only to describe a less usual form of presentation and its orientation but also to provide a modest literature review in a rather demanding pathology.

Apple Core Unveiled: Malignant Colonic Obstruction Revealing an Unknown Rectosigmoid Neoplasm With Foreign Body Impaction.

This case report highlights a rare clinical scenario of a 46-year-old male presenting with constipation and fecaloid vomiting due to an impacted chicken bone within an unidentified rectosigmoid neoplasm, leading to acute malignant colonic obstruction. Emergent exploratory laparotomy revealed an impacted chicken bone lodged in a previously unknown rectosigmoid tumor. An anatomopathological examination revealed a mucinous adenocarcinoma with clear margins and one pericolic metastatic lymph node. The postoperative period was uneventful, and the patient was proposed for adjuvant chemotherapy. The abrupt onset of symptoms allowed for an early diagnosis, emphasizing the unexpected association between foreign body impaction and incidental malignant obstruction. This case underscores the complexity of managing foreign body ingestion in the gastrointestinal tract and emphasizes the crucial role of diagnostic imaging in surgical planning. Furthermore, it draws attention to the potential occurrence of colorectal cancer in younger individuals, emphasizing the necessity for clinical vigilance and screening strategies beyond conventional age recommendations.

Glycoproteomic analysis of serum from patients with gastric precancerous lesions.

Gastric cancer is preceded by a carcinogenesis pathway that includes gastritis caused by Helicobacter pylori infection, chronic atrophic gastritis that may progress to intestinal metaplasia (IM), dysplasia, and ultimately gastric carcinoma of the more common intestinal subtype. The identification of glycosylation changes in circulating serum proteins in patients with precursor lesions of gastric cancer is of high interest and represents a source of putative new biomarkers for early diagnosis and intervention. This study applies a glycoproteomic approach to identify altered glycoproteins expressing the simple mucin-type carbohydrate antigens T and STn in the serum of patients with gastritis, IM (complete and incomplete subtypes), and control healthy individuals. The immunohistochemistry analysis of the gastric mucosa of these patients showed expression of T and STn antigens in gastric lesions, with STn being expressed only in IM. The serum glycoproteomic analysis using 2D-gel electrophoresis, Western blot, and MALDI-TOF/TOF mass spectrometry led to the identification of circulating proteins carrying these altered glycans. One of the glycoproteins identified was plasminogen, a protein that has been reported to play a role in H. pylori chronic infection of the gastric mucosa and is involved in extracellular matrix modeling and degradation. Plasminogen was further characterized and showed to carry STn antigens in patients with gastritis and IM. These results provide evidence of serum proteins displaying abnormal O-glycosylation in patients with precursor lesions of gastric carcinoma and include a panel of putative targets for the non-invasive clinical diagnosis of individuals with gastritis and IM.

Fournier Gangrene Management: Is a Stoma Mandatory?

Fournier gangrene is a rare life-threatening surgical emergency mainly due to a polymicrobial infection of the perineal, genital, or perianal region. It is characterized by rapid tissue destruction and systemic signs of toxicity. It is more frequent in males and immunocompromised patients, such as patients with poorly controlled diabetes, alcoholism, or human immunodeficiency virus (HIV) infection. Treatment often involves surgical intervention, broad-spectrum antibiotic therapy, fecal diversion surgery, and negative pressure wound therapy (NPWT). Delays in diagnosis are associated with high mortality due to rapid progression to septic shock.

Jejunal Gastrointestinal Stromal Tumor: A Strange Cause of Massive Gastrointestinal Bleeding.

Jejunal gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors of the gastrointestinal (GI) tract and a rare cause of massive GI bleeding. Due to this rarity and non-specific presentation, diagnosis and treatment may be difficult and often delayed. Urgent surgical intervention is crucial for controlling the source of bleeding and total tumor excision. Herein, we present the case of a 40-year-old male who presented to the emergency room (ER) with features of upper GI bleeding. He referred astheny and black stools, and was pale, sweaty, and tachycardic despite normal blood pressure. Rectal examination revealed melena, and laboratory findings revealed decreased hemoglobin (Hb) and elevated blood urea. Upper endoscopy was normal, and the Hb level dropped again to 6.9 g/dL; therefore, blood transfusion was required during ER observation. For further investigation, the patient underwent an angio-computed tomography scan, which revealed a lesion located in a jejunal loop as the probable bleeding source. Emergency exploratory laparotomy revealed a jejunal loop tumor. Segmental enterectomy containing the tumor was performed and the post-operative period was uneventful. The anatomopathological examination was compatible with low-risk GIST, and the multidisciplinary board agreed that surveillance was the best ongoing treatment. Due to the rarity of jejunal GIST as the cause of massive GI bleeding, diagnosis may be challenging, delaying prompt treatment with bleeding source control. In such cases, surgery may be both lifesaving and curative. Therefore, these tumors should not be forgotten when managing patients with occult GI bleeding with an atypical presentation to prevent delays in treatment and severe outcomes.

Buerger's Disease - A Clinical Case.

Buerger's disease is a distal segmental nonatherosclerotic vasculopathy that involves the inferior and superior limbs of smoker males younger than 45 years old. This article aims to describe a clinical case and revise the literature about Buerger's disease. A 45-year-old smoker male repeatedly visited the emergency department for refractory pain and inflammatory signs in the right hallux. After developing ulcers in the right foot, Doppler ultrasonography revealed segmental occlusion of distal arteries of that limb. It was also observed in arteriography "corkscrew" collaterals. Autoimmune, thrombophilic and cardiovascular diseases were excluded. Analgesia, antibiotics and alprostadil were implemented. As a result, the patient stopped smoking and was submitted to minor amputation with complete healing, after which he remained asymptomatic. Buerger's disease is a diagnosis of exclusion. Therefore, smoking cessation is the most effective treatment and is crucial to prevent disease progression.

Breast cancer in young women: a rising threat: A 5-year follow-up comparative study.

Introduction: Breast cancer in young women is usually considered as breast cancer occurring in women younger than 40 years and is the most frequent cancer-related cause of death in these patients. In the past few years, there seems to be an increasing trend in the prevalence of breast cancer in young women, which, associated with poorer prognosis, more aggressive histologic features, and more frequent recurrence rates, makes it a rising threat to young women. This study aimed to evaluate the biological behavior of breast cancer in young women in our institution. Material and methods: A retrospective, unicentric, cohort study was conducted between 2012 and 2016. All consecutive patients with breast cancer were enrolled in the study. Cases were divided into two groups: case group, those younger than 40 years, and control group, those 40 years or older. The exclusion criterion was nonoperative treatment. Several clinical and pathologic parameters were evaluated, as well as were overall survival time and disease-free survival time. Results: The incidence of breast cancer in young women presented a rising tendency over the study period. Significant differences were observed in the comparison of the groups according to body mass index, age at menarche, age at birth of the first child, and proliferation rate. There were no differences in overall survival and disease-free survival rates between the groups. Conclusions: Young women had a more symptomatic presentation, a greater tumor proliferation rate, but similar outcomes compared with older patients. Greater multicentric studies are needed to confirm or refute these results.

CDX2 autoregulation in human intestinal metaplasia of the stomach: impact on the stability of the phenotype.

BACKGROUND AND AIMS: Intestinal metaplasia (IM) is a gastric preneoplastic lesion that appears following Helicobacter pylori infection and confers an increased risk for development of cancer. It is induced by gastric expression of the intestine-specific transcription factor CDX2. The regulatory mechanisms involved in triggering and maintaining gastric CDX2 expression have not been fully elucidated. The Cdx2(+/-) mouse develops intestinal polyps with gastric differentiation and total loss of Cdx2 expression in the absence of structural loss of the second allele, suggesting a regulatory defect. This putative haplo-insufficiency, together with the apparent stability of IM, led to the hypothesis that CDX2 regulates its own expression through an autoregulatory loop in both contexts. METHODS: Gastrointestinal cell lines were co-transfected with wild-type or mutated Cdx2 promoter constructs and CDX2 expression vector for luciferase assays. Transfection experiments were also used to assess endogenous CDX2 autoregulation, evaluated by RT-PCR, qPCR and western blotting. Chromatin immunoprecipitation was performed in a cell line, mouse ileum and human IM. RESULTS: CDX2 binds to and transactivates its own promoter and positively regulates its expression in gastrointestinal human carcinoma cell lines. Furthermore, CDX2 is bound to its promoter in the mouse ileum and in human gastric IM, providing a major contribution to understanding the relevance of this autoregulatory pathway in vivo. CONCLUSION: The results of this study demonstrate another layer of complexity in CDX2 regulation by an effective autoregulatory loop which may have a major impact on the stability of human IM, possibly resulting in the inevitable progression of the gastric carcinogenesis pathway.

Handlebar hernia-unusual complication from blunt trauma.

Handlebar hernia is a rare entity, mainly resulting from blunt abdominal trauma with a sudden deceleration mechanism. Diagnosis of handlebar at admission may be difficult because the rupture of abdominal wall layers often is not clinically recognized in the emergency department, which requires a high degree of suspicion to identify theses lesions. It is very important to rule out the presence of intra-abdominal injuries, and in adults, surgical repair is needed. Herein, the case of an adult man who presented to the emergency department with blunt abdominal trauma caused by a motorcycle handlebar is described.

Primary cutaneous B-cell lymphoma arising from an inguinal hernioplasty scar.

The primary cutaneous B-cell lymphoma (PCBCL) is a rare neoplasm. It is believed that antigenic stimulation and chronic inflammation can be the basis of pathogenesis. Here, we report a case that to our knowledge is the first patient with a presentation of a PCBCL arising from a surgical scar, in particular, an inguinal hernioplasty. The case reminds us of the importance of raising clinical suspicion for malignant neoplasms in surgical scars, in particular, after mesh placement. MeSH terms: 'lymphoma, large b-cell, diffuse', 'skin' and 'cicatrix'.

Recurrence of Graves' disease in the thyroglossal duct after total thyroidectomy.

Graves' disease (GD) due to hyperfunction of thyroglossal duct remnants is rare, but recurrence after total thyroidectomy is even rarer. We present a rare case of a patient with recurrence of GD in a thyroglossal duct, after total thyroidectomy, who has been treated by Sistrunk procedure. Patients with a history of GD and difficult thyroid function control after total thyroidectomy should be studied to rule out persistent and functional thyroid tissue. In these cases, surgical treatment is an effective option.

Meckel's diverticulitis in a COVID-19 adult.

Meckel's diverticulitis is an unusual cause of acute abdomen condition in adults requiring prompt surgical treatment. We report a case of a 53-year-old male with coronavirus disease 19 (COVID-19), admitted to the emergency department with an acute abdominal pain. A computed tomography scan with intravenous contrast performed on the patient confirmed an inflamed short segment of the small bowel and the presence of a localized free peritoneal fluid. The definitive diagnosis was made intraoperatively, by means of an emergent ileal resection with primary anastomosis, which confirmed Meckel's diverticulitis. Postoperative evolution was ordinary. The association of COVID-19 with the acute abdomen is found to be weak, therefore surgical consultation is advised to minimize delayed treatment.