Synchronous Gastric and Colon Cancer.

Colorectal cancer (CRC) and gastric cancer, ranking as the third and fifth most prevalent global cancers, respectively, have seen increased diagnoses due to advancements in early detection and extended lifespans. Synchronous and metachronous cancers, with a rare incidence, are notable, with CRC being the predominant synchronous occurrence in gastric cancer patients. Screening CRC patients for gastric cancer is debated due to its low incidence, underscoring the crucial role of early diagnosis. Distinguishing between metastatic adenocarcinoma and synchronous tumors is challenging, relying on techniques such as immunohistochemistry. Surgery is the primary treatment for synchronous cancer, with successful single-stage surgeries reported. A case presentation of a 68-year-old female highlights these complexities. The final diagnosis encompassed stage I gastric cancer and stage IV colon cancer, leading to adjuvant chemotherapy. Synchronous gastric cancer and CRC present a unique clinical challenge, necessitating tailored approaches. Collaboration between surgical and oncological teams is crucial for comprehensive treatment planning and optimizing patient outcomes.

Coexistence of Acute Appendicitis and Sigmoid Diverticulitis.

In recent years, there has been a notable increase in acute diverticulitis cases, attributed to modern lifestyles and improved diagnostic techniques. We present a rare case of concurrent acute appendicitis and diverticulitis in a 35-year-old male who came to the emergency department with abdominal pain. While appendicitis typically requires surgery, diverticulitis is often managed conservatively. Computed tomography is key in diagnosis and decision-making. Despite their differing treatments, cases like this challenge the perception of their rarity. This case prompts consideration of multifocal abdominal pathology. Recognizing concurrent appendicitis and diverticulitis is crucial for guiding appropriate diagnostic and treatment strategies, potentially including non-operative management in select cases.

Video-Assisted Endoscopic Inguinal Lymph Node Dissection for Acral Melanoma.

This article discusses acral melanoma, a rare subtype of melanoma often presented at the later stages of the disease and is, thus, associated with poor survival rates, especially in patients with a lower socioeconomic status. Surgical resection is the primary treatment option for localized acral melanoma, while amputation is often necessary for tumors on the digits or the midfoot. Lymphadenectomy may be necessary for patients with regional lymph node involvement; however, the therapeutic role of dissection remains controversial. Here, we present the case of a 68-year-old man with acral melanoma who underwent a Lisfranc amputation and endoscopic groin lymph node dissection for ganglionic metastasis. In Ecuador, this is the first reported case of endoscopic groin lymphadenectomy for regional lymph node metastasis secondary to acral melanoma. The discussion explores the role of sentinel lymph node biopsy and the completion of lymph node dissection in managing regional lymph nodes in melanoma patients. This case study aims to contribute to the growing knowledge on acral melanoma, assess the need for better patient care, and analyze the role of minimally invasive techniques for inguinal lymph node dissections.

Collision Tumor of the Appendix.

This report discusses the case of a 20-year-old female patient who presented with acute abdominal pain, nausea, and vomiting. Initial laboratory analyses suggested an inflammatory process, but imaging studies failed to reveal pathologies. The patient underwent a diagnostic laparoscopy, which showed a thickened and multicystic appendix with signs of acute inflammation. Pathology indicated a positive cytology for malignancy, with a grade 1 mixed well-differentiated neuroendocrine tumor (NET) and high-grade mucinous neoplasm identified in the middle and distal thirds of the appendix. Finding both tumors in the same patient is extremely rare and has been reported in a few cases. The case emphasizes the importance of considering appendiceal tumors in the differential diagnosis of acute abdominal pain, even in young patients, and highlights the value of laparoscopy in their diagnosis. The early detection and appropriate management of appendiceal tumors are crucial for improving patient outcomes.

Synchronous Acute Appendicitis and Acute Cholecystitis.

The occurrence of synchronous acute cholecystitis and appendicitis is rare. There are few cases reported and small series in the literature. We report the case of a 77-year-old male who presented to the emergency department with right-sided abdominal pain. He was diagnosed preoperatively with acute calculous cholecystitis. During the initial laparoscopy, a complicated appendiceal phlegmon was found and was treated with a one-step laparoscopic approach and subsequent antibiotics. The patient had an uneventful recovery and was discharged on postoperative day (POD) 2. The pathology report confirmed both diagnoses and an incidental low-grade appendiceal mucinous neoplasm. Although uncommon, it is important to be aware of the possibility of both simultaneous pathologies in a patient who presents to the emergency department with abdominal pain.

Jejunal Gastrointestinal Stromal Tumor: A Diagnostic Challenge.

Gastrointestinal stromal tumors (GISTs) are a common type of soft tissue sarcoma that originates from the interstitial cells of Cajal in the gastrointestinal (GI) tract. These tumors usually affect people above 50 years of age and can be difficult to diagnose, as symptoms can be vague and nonspecific, with some patients remaining asymptomatic. Early diagnosis and treatment are crucial because GISTs can be aggressive and may metastasize. We present a case of a 74-year-old man who presented to our hospital with GI bleeding and anemia. Despite initial investigations, the source of bleeding was not identified until capsule endoscopy and then balloon enteroscopy revealed an ulcerated mass in the jejunum. The tumor was successfully removed using a minimally invasive laparoscopic approach, and the histopathologic report confirmed the diagnosis of GIST. The patient had an uneventful postoperative course. This case highlights the importance of considering GISTs in the differential diagnosis of obscure GI bleeding. A multidisciplinary approach is essential to ensure the best outcomes for these patients. Additionally, the use of minimally invasive surgery should be considered whenever possible to minimize postoperative complications and promote faster recovery.

Perforated Meckel's Diverticulum Caused by a Toothpick: A Case Report and Review of Literature.

Although Meckel's diverticulum is the most common congenital anomaly of the gastrointestinal tract, it is rare in the general adult population. When it does become symptomatic, it is usually due to complications such as perforation. We report the case of a 38-year-old man who presented with acute abdominal pain in the right iliac fossa, fever, and tachycardia. Complementary exams at the emergency department showed leukocytosis and elevated C-reactive protein. Acute appendicitis was suspected, so he was taken to the operating room for a diagnostic laparoscopy. During surgical exploration, a perforated Meckel's diverticulum caused by a toothpick was found. Surgery was converted to laparotomy with resection of the small bowel segment containing the diverticulum, followed by a primary anastomosis. The postoperative period was uneventful, and the patient was discharged on day seven. No abnormalities were reported in the histopathology study. In this report, we review and discuss similar cases found in the literature, all of them male with acute abdomen and suspicion of appendicitis. We aim to remark on the importance of keeping in the differential of such patients a perforated Meckel's diverticulum.

GLI1 interaction with p300 modulates SDF1 expression in cancer-associated fibroblasts to promote pancreatic cancer cells migration.

Carcinoma-associated fibroblasts (CAFs) play an important role in the progression of multiple malignancies. Secretion of cytokines and growth factors underlies the pro-tumoral effect of CAFs. Although this paracrine function has been extensively documented, the molecular mechanisms controlling the expression of these factors remain elusive. In this study, we provide evidence of a novel CAF transcriptional axis regulating the expression of SDF1, a major driver of cancer cell migration, involving the transcription factor GLI1 and histone acetyltransferase p300. We demonstrate that conditioned media from CAFs overexpressing GLI1 induce the migration of pancreatic cancer cells, and this effect is impaired by an SDF1-neutralizing antibody. Using a combination of co-immunoprecipitation, proximity ligation assay and chromatin immunoprecipitation assay, we further demonstrate that GLI1 and p300 physically interact in CAFs to co-occupy and drive SDF1 promoter activity. Mapping experiments highlight the requirement of GLI1 N-terminal for the interaction with p300. Importantly, knockdowns of both GLI1 and p300 reduce SDF1 expression. Further analysis shows that knockdown of GLI1 decreases SDF1 promoter activity, p300 recruitment, and levels of its associated histone marks (H4ac, H3K27ac, and H3K14ac). Finally, we show that the integrity of two GLI binding sites in the SDF1 promoter is required for p300 recruitment. Our findings define a new role for the p300-GLI1 complex in the regulation of SDF1, providing new mechanistic insight into the molecular events controlling pancreatic cancer cells migration.

Nuclear Dynamics and Chromatin Structure: Implications for Pancreatic Cancer.

Changes in nuclear shape have been extensively associated with the dynamics and functionality of cancer cells. In most normal cells, nuclei have a regular ellipsoid shape and minimal variation in nuclear size; however, an irregular nuclear contour and abnormal nuclear size is often observed in cancer, including pancreatic cancer. Furthermore, alterations in nuclear morphology have become the 'gold standard' for tumor staging and grading. Beyond the utility of altered nuclear morphology as a diagnostic tool in cancer, the implications of altered nuclear structure for the biology and behavior of cancer cells are profound as changes in nuclear morphology could impact cellular responses to physical strain, adaptation during migration, chromatin organization, and gene expression. Here, we aim to highlight and discuss the factors that regulate nuclear dynamics and their implications for pancreatic cancer biology.

Genomic and Epigenomic Landscaping Defines New Therapeutic Targets for Adenosquamous Carcinoma of the Pancreas.

Adenosquamous cancer of the pancreas (ASCP) is a subtype of pancreatic cancer that has a worse prognosis and greater metastatic potential than the more common pancreatic ductal adenocarcinoma (PDAC) subtype. To distinguish the genomic landscape of ASCP and identify actionable targets for this lethal cancer, we applied DNA content flow cytometry to a series of 15 tumor samples including five patient-derived xenografts (PDX). We interrogated purified sorted tumor fractions from these samples with whole-genome copy-number variant (CNV), whole-exome sequencing, and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) analyses. These identified a variety of somatic genomic lesions targeting chromatin regulators in ASCP genomes that were superimposed on well-characterized genomic lesions including mutations in TP53 (87%) and KRAS (73%), amplification of MYC (47%), and homozygous deletion of CDKN2A (40%) that are common in PDACs. Furthermore, a comparison of ATAC-seq profiles of three ASCP and three PDAC genomes using flow-sorted PDX models identified genes with accessible chromatin unique to the ASCP genomes, including the lysine methyltransferase SMYD2 and the pancreatic cancer stem cell regulator RORC in all three ASCPs, and a FGFR1-ERLIN2 fusion associated with focal CNVs in both genes in a single ASCP. Finally, we demonstrate significant activity of a pan FGFR inhibitor against organoids derived from the FGFR1-ERLIN2 fusion-positive ASCP PDX model. Our results suggest that the genomic and epigenomic landscape of ASCP provide new strategies for targeting this aggressive subtype of pancreatic cancer. SIGNIFICANCE: These data provide a unique description of the ASCP genomic and epigenomic landscape and identify candidate therapeutic targets for this dismal cancer.

GLI1/GLI2 functional interplay is required to control Hedgehog/GLI targets gene expression.

The Hedgehog-regulated transcription factors GLI1 and GLI2 play overlapping roles in development and disease; however, the mechanisms underlying their interplay remain elusive. We report for the first time that GLI1 and GLI2 physically and functionally interact in cancer cells. GLI1 and GLI2 were shown to co-immunoprecipitate in PANC1 pancreatic cancer cells and RMS13 rhabdomyosarcoma cells. Mapping analysis demonstrated that the zinc finger domains of both proteins are required for their heteromerization. RNAi knockdown of either GLI1 or GLI2 inhibited expression of many well-characterized GLI target genes (BCL2, MYCN, PTCH2, IL7 and CCND1) in PANC1 cells, whereas PTCH1 expression was only inhibited by GLI1 depletion. qPCR screening of a large set of putative canonical and non-canonical Hedgehog/GLI targets identified further genes (e.g. E2F1, BMP1, CDK2) strongly down-regulated by GLI1 and/or GLI2 depletion in PANC1 cells, and demonstrated that ANO1, AQP1 and SOCS1 are up-regulated by knockdown of either GLI1 or GLI2. Chromatin immunoprecipitation showed that GLI1 and GLI2 occupied the same regions at the BCL2, MYCN and CCND1 promoters. Furthermore, depletion of GLI1 inhibited GLI2 occupancy at these promoters, suggesting that GLI1/GLI2 interaction is required for the recruitment of GLI2 to these sites. Together, these findings indicate that GLI1 and GLI2 co-ordinately regulate the transcription of some genes, and provide mechanistic insight into the roles of GLI proteins in carcinogenesis.

Case of lung carcinoma revealed by vulvar metastasis associated with systemic scleroderma and literature review.

UNLABELLED: Metastatic carcinoma to the vulva is rare, where the incidence is believed to be between 5% and 8%. However, malignant tumors have been described in 3-11% of systemic scleroderma (SSc) cases. We report the case of one patient, a 66-year-old postmenopausal woman, whose medical history was marked with rheumatic vascular disease (systemic scleroderma) since 1993 without muscular, renal, cardiac lesions or HTA (arterial hypertension) and without tobacco history. The woman presented with a new vulvar mass of the right labia in December 2011 that had progressively enlarged in size. CT scan of the abdominopelvic region demonstrated a lobular mass of the right labia with central necrosis, 7 cm on the wide axis, and the rectum and the vaginal wall were normal. No inguinal or iliac lymphadenopathy was noted. An outpatient excisional biopsy revealed a poorly differentiated malignant tumor suggestive of carcinoma. IHC: CK7+/CK20-, estrogen receptors-, AE 1 AE 3+, vimentine+, S100-, Desmina-, CD34-, KI 67: 20%. The thoracic scan revealed a large mass of 4 cm × 3 cm in the right lung base with right paratracheal lymphadenopathy 3 cm × 2 cm. A bronchoscopy revealed discrete stenosis of the mediastinal portion of the right bronchial tree. The bronchial biopsy also revealed poorly differentiated lung carcinoma, non-small cell, which was identical with the vulvar tumor. CONCLUSION: The presence of the single lung lesion with only one lymphadenopathy paratracheal with pathological and immunohistochemical (IHC) profile similar to the vulvar lesion, and a particular IHC profile with CK7+ and CK20- was detected - that is more specific to the primitive pulmonary cancer, and the presence of only one sarcoma marker vementine+, desmine and actine-. Also the presence of KI 67: 20%, predicted the proliferative and great metastatic power of the lung tumor was observed. Additionally, lung cancer was the most frequent type and may develop in scleroderma as reported in most studies. This allows to conclude for primitive lung carcinoma revealed with vulvar metastasis after elimination of the possibility of vulvar sarcoma. The patient was treated by chemotherapy (Taxol/Platin) with partial response from the lung after 3 cycles and palliative radiotherapy in the vulva with a good response. This case described primary lung carcinoma associated with scleroderma, revealed by a vulvar metastasis, which may be related to the aggressiveness of lung cancer when the lung fibrosis follow-up is not performed well to detect early the development of lung tumors in the patient with systemic scleroderma.

Le carcinome métastatique de la vulve est rare, son incidence est estimé entre 5% et 8%. D'autre part les tumeurs malignes ont été décrite dans 3-11% de la sclérodermie systémique (ScS) cas. Nous rapportons le cas d'une patiente, 66 ans ménopausée, ses antécédents médicaux ont été marquée par une maladie vasculaire rhumatismale (sclérodermie systémique) depuis 1993 sans atteintes musculaires, rénales, cardiaques ou HTA (hypertension artérielle) et sans histoiretabagique. La patiente a représenté une masse vulvaire de la lèvre droite de la vulve en Décembre 2011, qui avait progressivement augmenté de taille. La tomodensitométrie abdomino-pelvienne a montré une masse lobulaire de la lèvre droite avec une nécrose centrale, 7 cm l'axe le plus large, le rectum et la paroi vaginale étaient normale. Aucune adénopathie inguinale ou iliaque a été noté. Une biopsie-exérèse ambulatoire a révélé une tumeur maligne peu différenciée suggérant un cancer. IHC: CK7+/CK20−, récepteurs des oestrogènes−, AE 1 AE 3+, vimentine+, S100−, Desmina−, CD34−, KI 67: 20%. Le scanner thoracique a révélé une grosse masse de 4 × 3 cm au niveau de la base du poumon droit avec lymphadénopathie paratrachéaux droite de 3 × 2 cm. Une bronchoscopie a révélé: une sténose de la partie médiastinale de l'arbre bronchique droit. Et la biopsie bronchique a révélé un carcinome du poumon peu différencié, non à petites cellules, ce qui était identique à la tumeur vulvaire. CONCLUSION: La présence de la lésion pulmonaire unique avec un seul lymphadénopathie paratrachéal avec à l'anatomopathologie et immunohistochimie (IHC) un profil similaire à la lésion vulvaire, et le profil IHC particulier avec CK7+ et CK20− qui sont plus spécifiques au cancer primitif pulmonaire, et la présence d'un seul marqueur de sarcome vementine+, desmine et actine−. Aussi la présence de KI 67: 20%, qui prédit le grand pouvoir prolifératif et métastatique de la tumeur pulmonaire. En plus le cancer du poumon est le type de cancer le plus fréquent qui peut se développer chez les patients sclérodermiques dans la plupart des études. Ces arguments ont permis de conclure au carcinome primitif du poumon révélé par des métastases vulvaire après élimination de la possibilité de sarcome vulvaire. Traités par chimiothérapie (Taxol/Platin) avec une réponse partielle au niveau du poumon après 3 cycles et radiothérapie palliative de la vulve avec une bonne réponse. Ce cas décrit un carcinome primitif du poumon associé à une sclérodermie systémique, révélé par une métastase vulvaire, qui peut être lié à l'agressivité du cancer pulmonaire lorsque le bon suivi de la fibrose pulmonaire n'est pas effectué pour le dépistage précoce des tumeurs pulmonaires développées chez des patients suivis pour sclérodermie systémique.