A giant pelvic infiltrating schwannoma misdiagnosed as an ovarian neoplasm that was resected using a laparoscopic approach: A case report.

Introduction and importance: Large retroperitoneal schwannomas are rare and present significant challenges in surgical management, particularly when located in the pelvic region. Gynecologists can encounter rare problems when a pelvic schwannoma is mistaken for an adnexal pathology. Case Presentation: A 62-year-old woman presented with a giant retroperitoneal mass suspected of a potentially malignant ovarian tumor preoperatively. Computed tomography revealed a large mixed solid-cystic mass near the right adnexa measuring 118 × 100 × 80 mm. The cancer antigen 125 level was 196 U/mL. We performed a diagnostic-operative laparoscopy, which showed a retroperitoneal neoformation below the cava and aortic bifurcation adherent to the sacrum, right pelvic vessels, and hypogastric nerve up to the vagina. We carefully detached the mass from the nearby tissues using the most appropriate laparoscopic devices. The entire neoplasm was removed through the vagina into a surgical bag. The surgery lasted 180 min without complications. Histology revealed a grade I benign schwannoma. At the 12-month follow-up, the patient was asymptomatic without signs of recurrence. Clinical Discussion: Pelvic retroperitoneal schwannomas can mimic ovarian carcinomas; misdiagnosis may occur due to their rarity and the difficulty of interpreting preoperative imaging. In case of unexpected giant presacral schwannomas surgical management is challenging due to their peculiar location. Conclusion: This case underscores the need for a skilled, experienced team of gynecological oncologists to achieve favorable outcomes when performing laparoscopic surgery of giant pelvic retroperitoneal schwannoma. Adequate knowledge of the complex pelvic anatomy, careful surgical planning, and familiarity with the most appropriate surgical tools are critical points.

Environmental Influence on the Occurrence of Multi-Organ Cystic Echinococcosis Infection in a Patient from Sardinia, Italy.

An uncommon clinical case of an adult woman who was referred to the hospital with severe symptoms attributable to cystic echinococcosis (CE) is described in this report. According to a questionnaire, the subject was exposed to a high risk of infection since she was employed on a farm about 20 years before diagnosis. She lived close to several animal species and handled vegetables in inadequate hygienic conditions. Medical and laboratory investigations confirmed the presence of massive echinococcal cystic lesions in each lung and in the liver. Given the peculiarity of the case, pharmacological and surgical treatments were the only conceivable option. The association of pharmacological treatment, surgery, and interventional radiology procedure represented a reliable and effective way to handle a complex case of human hydatidosis. A multi-disciplinary approach was mandatory, resulting in a clear and conclusive diagnosis of CE caused by the zoonotic parasite E. granulosus sensu stricto of the G1 genotype.

Pathogenic and Prognostic Roles of Paraneoplastic Leukocytosis in Cervical Cancer: Can Genomic-Based Targeted Therapies Have a Role? A Literature Review and an Emblematic Case Report.

Tumor-associated leukocytosis has been associated with poor prognosis in cervical cancer. Leukemoid reaction (i.e., white blood cell count > 40,000/µL) is defined paraneoplastic (PLR) when it occurs in the presence of a cytokine-secreting tumor (CST) without neoplastic bone marrow infiltration. Cervical cancers displaying PLR represent a peculiar entity characterized by a rapidly progressive behavior typically associated with chemo-radioresistance. The present paper aims to review the literature about the pathogenetic mechanisms of PLR and its prognostic role in cervical cancer. Moreover, it reports the emblematic case of a patient with an advanced cervical cancer associated with PLR that was chemotherapy resistant. The patient underwent a palliative cytoreductive surgery of high complexity, obtaining a temporary regression of PLR. The tumor sample stained positive for G-CSF and IL-6, thus indicating a CST. Notably, the tumor genomic analysis revealed a PI3CKA mutation. Therefore, at the instrumental evidence of a rapidly progressive disease relapse, which was accompanied by reappearance of PLR, we started a targeted treatment with a selective PIK3 inhibitor alpesilib combined with the JAK1-2 inhibitor ruxolitinib. We achieved a relief of symptoms and leukocytosis; however, severe side effects necessitated the treatment suspension. In conclusion, as therapeutic strategies for cancer with PLR are scarcely reported in literature, our study could contribute to expand our understanding of the topic and provide a basis for further research.

Diagnostic Framework of Pelvic Massive Necrosis with Peritonitis following Chemoradiation for Locally Advanced Cervical Cancer: When Is the Surgery Not Demandable? A Case Report and Literature Review.

Concurrent platinum-based chemoradiation (CCRT) is the established treatment for locally advanced cervical cancer and has an acceptable toxicity. Radiation-induced necrosis of the uterus and pelvic tissue is a rare and usually late potential complication. Limited data are available about its management. Here, we describe a case of a patient affected by a locally advanced cervical cancer (stage IVA) who received CCRT, obtaining a partial response with persistence of bladder and rectal infiltration. Unfortunately, after the first brachytherapy dose, the patient developed a worsening clinical picture with fever and altered laboratory data indicative of sepsis; the computed tomography revealed a massive necrosis of the uterus with pelvic abscess and peritonitis. We performed a laparoscopic emergency surgery with removal of the necrotic tissue, supracervical hysterectomy, bilateral-oophorectomy, and abscess drainage. Thereafter, once the severe inflammatory condition was resolved, the patient underwent pelvic exenteration with palliative/curative intent. The postoperative PET/CT was negative for residual disease. However, the patient needed further hospitalization for re-occurrence of peritonitis with multiple abscesses. A careful diagnosis is crucial in locally advanced cervical cancer patients who, after CCRT, present persistent pain and problematic findings at imaging and laboratory parameters. In these cases, radiation-induced necrosis of the pelvis should be suspected. This case helps to clarify the central role of surgery, especially when actinic necrosis leads to complications such as abscess, fistulae, and extensive tissue destruction that cannot be conservatively medically handled. Laparoscopy represents an ideal approach to realizing the correct diagnosis, as well as enabling the performance of important therapeutic surgical procedures.

Refractory Chylothorax Secondary to Sizeable Azygos Vein Hemangioma: Tailored Multimodal Treatment of a Challenging Case Report.

BACKGROUND: Mediastinal hemangiomas are rare, and their etiology remains unclear. Most patients affected have no pathognomonic clinical symptoms, and the diagnosis is often incidental. Due to the paucity of the available literature regarding the management of this disease, the choice and timing of treatment remains controversial. CASE PRESENTATION: Herein, we report the case of a hemangioma of the azygos vein arch in a 66-year-old woman who presented with dyspnea, chest discomfort, dysphagia, and weight loss. A simultaneous right chylothorax refractory to conservative management was found. A CT-guided biopsy of the mass was performed, and it confirmed the vascular nature of the lesion. Therefore, the patient underwent an angiography followed by endo-vascular embolization. Three days later, thoracoscopic surgical resection of the mass and the repair of the chyle leakage were performed safely. The patient was discharged uneventfully on postoperative day seven, with complete resolution of all the presenting symptoms. CONCLUSIONS: Treatment of symptomatic mediastinal hemangiomas could be mandatory, but a thorough multidisciplinary approach to these rare malformations is essential. Despite the risk of intraoperative bleeding, selective endovascular embolization followed by thoracoscopic surgery allowed for a complete and safe resection with a good outcome.

Next-Generation Sequencing Whole-Genome Analysis for Targeted Treatment Approach of Metastatic Bartholin Gland Adenocarcinoma: An Emblematic Case Report and Review of the Literature.

Bartholin gland adenocarcinoma (BGA) is extremely rare and is characterized by high rates of lymph-node recurrence and distant metastases. No effective palliative treatments are available for metastatic BGA; therefore, advanced BGA remains a challenge for gynecologic oncologists. Considering the rarity of this disease and the lack of a standardized approach, the present study aims to discuss the available literature on current therapies for BGA and to describe an emblematic case treated with a novel tailored approach. A postmenopausal woman with advanced BGA was referred to our department for an adequate evaluation, staging and treatment. Notably, we used PET/CT as a fundamental imaging technique for staging and follow-up. The patient underwent primary surgery followed by standard chemotherapy and pelvic radiotherapy. Three months later, she relapsed, with the appearance of multiple metastatic sites. Considering the evident chemoresistance to standard chemotherapy and the absence of valid therapeutic alternatives for this rare cancer, she was treated with a combination of repeated minimally invasive surgical procedures for all the resectable metastatic lesions and innovative approaches comprising, firstly, chemoimmunotherapy with Nivolumab combined with metronomic vinorelbine, which resulted in a clinical response for approximately 7 months. Upon disease progression, we used a targeted systemic approach based on the whole genomic profile of the primary tumor, which showed PTEN loss, which is predictive of a benefit from an mTOR inhibitor, and a CCND1 amplification, which predicts sensitivity to CDK4/6 inhibitors. Therefore, she received Everolimus, resulting in a significant metabolic response that lasted 12 months. Thereafter, upon further progression of the disease, the patient started Palbociclib treatment, which is currently ongoing, with evidence of a metabolic response. The patient has survived for 54 months from diagnosis, with a good performance status. In conclusion, the present paper confirms the lack of efficacy of conventional therapeutic regimens in the context of advanced, recurrent or metastatic adenocarcinomas of the Bartholin gland. The case report shows how a personalized multidisciplinary approach based on repeated minimally invasive surgery and tailored anticancer treatment based on whole-genome sequencing analysis could be effective and associated with prolonged survival in this rare gynecological cancer.

Feasibility and safety of total laparoscopic hysterectomy for uteri weighing from 1.5 kg to 11.000 kg.

PURPOSE: To assess the feasibility and safety of total laparoscopic hysterectomy (TLH) for uteri ≥ 1.5 kg. METHODS: We prospectively evaluated all elective TLHs (with or without adnexectomy) performed for fibromatous uteri between August 2009 and August 2019 in the Department of Obstetrics and Gynecology, Sirai Hospital, Carbonia, and the Department of Gynecologic Oncology, Businco Hospital, Azienda Ospedaliera Brotzu, Cagliari. Patients with large myomatous uteri (uterine weight ≥ 1.5 kg on pathology reports) were included in the analysis. We examined all procedures and collected data about intra- and post-operative short-term and long-term complications, intraoperative blood loss, operative time, hospital stay, and time to achieve well-being. RESULTS: Seventy-eight patients were included. The median weight was 2,000 g (range 1,500-11,000 g), estimated blood loss was 100 mL (range 10-700 mL), operating time was 135 min (range 60-300 min), and hospital stay was 2 days (range 2-5 days). Conversion to laparotomy occurred in 4 patients (5.1%) with uterine weight ranging from 3 to 5.5 kg, due to severe adherence syndrome or inadequate visualization. As for intraoperative complications, 1 patient (who had the largest removed uterus weighing 11,000 g) experienced an intraoperative ureteral injury (grade III). No major postoperative complications occurred. CONCLUSIONS: This study provides the largest case series of TLH for fibromatous uteri > 1.5 kg and includes some of the largest uteri reported to date in the literature (weighing 5,320, 5,720, and 11,000 g, respectively). The study reaffirms the feasibility and safety of a minimally invasive hysterectomy even in the case of abnormally large uteri.

Retrospective outcomes analysis of 99 consecutive uniportal awake lung biopsies: a real standard of care?

BACKGROUND: Surgical lung biopsy for interstitial lung disease (ILD) is traditionally performed through video-assisted thoracic surgery (VATS) and general anesthesia (GA). The mortality and morbidity rates associated with this procedure are not negligible, especially in patients with significant risk factors and respiratory impairment. Based on these considerations, our center evaluated a safe non-intubated VATS approach for lung biopsy performed in ILD subjects. METHODS: Ninety-nine patients affected by undetermined ILD were enrolled in a retrospective cohort study. In all instances, lung biopsies were performed using a non-intubated VATS technique, in spontaneously breathing patients, with or without intercostal nerve blockage. The primary end-point was the diagnostic yield, while surgical and global operating room times, post-operative length of stay (pLOS), numeric pain rating scale (NPRS) after surgery and early mortality were considered as secondary outcomes. RESULTS: All the procedures were carried out without conversion to GA. The pathological diagnosis was achieved in 97 patients with a diagnostic yield of 98%. The mean operating room length-of-stay and operating time were 73.7 and 42.5 min, respectively. Mean pLOS was 1.3 days with a low readmissions rate (3%). No mortality in the first 30 days due to acute exacerbation of ILD occurred. Both analgesia methods resulted in optimal feasibility with a mean NPRS score of 1.13. CONCLUSIONS: In undetermined ILD patients, surgical lung biopsy with a non-intubated VATS approach and spontaneous ventilation anesthesia appears to be both a practical and safe technique with an excellent diagnostic yield and high level of patient satisfaction.

Laparoscopic management of a giant mucinous benign ovarian mass weighing 10150 grams: A case report.

BACKGROUND: Giant ovarian cysts (≥ 15 cm in diameter) are rare. The size limit of cysts and the methodology for a safe and successful minimally invasive surgery has not been established. Here we report a case of a large 10-kg multi-locular ovarian mass, which was successfully laparoscopically removed: Our aim was to innovate the surgical practice in this field by providing a safe, effective, and minimally invasive management method for such complex and rare cases. CASE SUMMARY: A 49-year-old nulliparous woman presented with abdominal distension, lasting from six Mo prior to admission; she reported worsening abdominal pain, abdominal swelling, and mild dyspnea. Imaging showed a presumed benign multi-locular (> 10 locules) left ovarian cyst that measured about 30 cm in diameter. Based on the IOTA-ADNEX model the mass had a 27.5% risk of being a borderline or malignant tumor. The patient was successfully treated via a direct laparoscopic approach with salpingo-oophorectomy, followed by the external drainage of the cyst. Tumor spillage was successfully avoided during this procedure. The final volume of the drained mucinous content was 8950 L; the cyst wall, extracted through the minilaparotomy, weighed about 1200 g. The pathologic gross examination revealed a 24 cm × 15 cm × 10 cm mass; the histologic examination diagnosed a mucinous cystoadenoma. To our knowledge, this is the first case of a giant multi-locular ovarian cyst treated with a direct laparoscopy with salpingo-oophorectomy followed by external decompression. CONCLUSION: Choosing the appropriate technique and surgeon skill are necessary for a safe and effective minimally-invasive approach of unique cases involving giant ovarian cysts.

Aluminum exposure and toxicity in neonates: a practical guide to halt aluminum overload in the prenatal and perinatal periods.

BACKGROUND: During the last years, human newborns have been overexposed to biologically reactive aluminum, with possible relevant consequences on their future health and on their susceptibility to a variety of diseases. Children, newborns and particularly preterm neonates are at an increased risk of aluminum toxicity because of their relative immaturity. DATA SOURCES: Based on recent original publications and classical data of the literatures, we reviewed the aluminum content in mother's food during the intrauterine life as well as in breast milk and infant formula during lactation. We also determined the possible role of aluminum in parenteral nutrition solutions, in adjuvants of vaccines and in pharmaceutical products. A special focus is placed on the relationship between aluminum overexposure and the insurgence of bone diseases. RESULTS: Practical points of management and prevention are suggested. Aluminum sources that infants may receive during the first 6 months of life are presented. In the context of prevention of possible adverse effects of aluminum overload in fetal tissues during development, simple suggestions to pregnant women are described. Finally, practical points of management and prevention are suggested. CONCLUSIONS: Pediatricians and neonatologists must be more concerned about aluminum content in all products our newborns are exposed to, starting from monitoring aluminum concentrations in milk- and soy-based formulas in which, on the basis of recent studies, there is still too much aluminum.

Thymosin ß4 expression in colorectal polyps and adenomas.

OBJECTIVE: Thymosin beta 4 (Tß4) is a ubiquitous peptide that plays pivotal roles in the cytoskeletal system and in cell differentiation. Recently, a role for Tß4 has been proposed in experimental and human carcinogenesis, including gastrointestinal cancer. This study was aimed at evaluating the relationship between Tß4 immunoreactivity and the initial steps of carcinogenesis. METHODS: In total, 60 intestinal biopsies, including 10 hyperplastic polyps, 10 sessile serrated adenomas/polyps, 15 colorectal adenomas with low-grade dysplasia, 15 adenomas with high-grade dysplasia, 15 adenocarcinomas and 10 samples of normal colon mucosa, were analyzed for Tß4 expression by immunohistochemistry. RESULTS: Weak cytoplasmic reactivity for Tß4 was detected in the normal colon mucosa. No reactivity for Tß4 was found in hyperplastic and sessile serrated polyps/adenomas. Tß4 expression was observed in 10/15 colorectal adenocarcinomas. In adenomas with low-grade dysplasia, Tß4 immunoreactivity was mainly detected in dysplastic glands but was absent in hyperplastic glands. Tß4 immunoreactivity was characterized by spot-like perinuclear staining. In high-grade dysplastic polyps, immunostaining for Tß4 appeared diffuse throughout the entire cytoplasm of dysplastic cells. Spot-like perinuclear reactivity was detected in adenocarcinoma tumor cells. CONCLUSIONS: Our study shows for the first time that Tß4 is expressed during different steps of colon carcinogenesis. The shift of Tß4 immunolocalization from low-grade to high-grade dysplastic glands suggests a role for Tß4 in colorectal carcinogenesis. However, the real meaning of Tß4 reactivity in dysplastic intestinal epithelium remains unknown.

Factors influencing the development of a personal tailored microbiota in the neonate, with particular emphasis on antibiotic therapy.

In recent years, it has been clearly evidenced that most cells in a human being are not human: they are microbial, represented by more than 1000 microbial species. The vast majority of microbial species give rise to symbiotic host-bacterial interactions that are fundamental for human health. The complex of these microbial communities has been defined as microbiota or microbiome. These bacterial communities, forged over millennia of co-evolution with humans, are at the basis of a partnership with the developing human newborn, which is based on reciprocal molecular exchanges and cross-talking. Recent data on the role of the human microbiota in newborns and children clearly indicate that microbes have a potential importance to pediatrics, contributing to host nutrition, developmental regulation of intestinal angiogenesis, protection from pathogens, and development of the immune system. This review is aimed at reporting the most recent data on the knowledge of microbiota origin and development in the human newborn, and on the multiple factors influencing development and maturation of our microbiota, including the use and abuse of antibiotic therapies.

Thymosin ß4 expression in colorectal polyps and adenomas

OBJECTIVE: Thymosin beta 4 (Tβ4) is a ubiquitous peptide that plays pivotal roles in the cytoskeletal system and in cell differentiation. Recently, a role for Tβ4 has been proposed in experimental and human carcinogenesis, including gastrointestinal cancer. This study was aimed at evaluating the relationship between Tβ4 immunoreactivity and the initial steps of carcinogenesis. METHODS: In total, 60 intestinal biopsies, including 10 hyperplastic polyps, 10 sessile serrated adenomas/polyps, 15 colorectal adenomas with low-grade dysplasia, 15 adenomas with high-grade dysplasia, 15 adenocarcinomas and 10 samples of normal colon mucosa, were analyzed for Tβ4 expression by immunohistochemistry. RESULTS: Weak cytoplasmic reactivity for Tβ4 was detected in the normal colon mucosa. No reactivity for Tβ4 was found in hyperplastic and sessile serrated polyps/adenomas. Tβ4 expression was observed in 10/15 colorectal adenocarcinomas. In adenomas with low-grade dysplasia, Tβ4 immunoreactivity was mainly detected in dysplastic glands but was absent in hyperplastic glands. Tβ4 immunoreactivity was characterized by spot-like perinuclear staining. In high-grade dysplastic polyps, immunostaining for Tβ4 appeared diffuse throughout the entire cytoplasm of dysplastic cells. Spot-like perinuclear reactivity was detected in adenocarcinoma tumor cells. CONCLUSIONS: Our study shows for the first time that Tβ4 is expressed during different steps of colon carcinogenesis. The shift of Tβ4 immunolocalization from low-grade to high-grade dysplastic glands suggests a role for Tβ4 in colorectal carcinogenesis. However, the real meaning of Tβ4 reactivity in dysplastic intestinal epithelium remains unknown. .

Cellular trafficking of thymosin beta-4 in HEPG2 cells following serum starvation.

Thymosin beta-4 (Tß4) is an ubiquitous multi-functional regenerative peptide, related to many critical biological processes, with a dynamic and flexible conformation which may influence its functions and its subcellular distribution. For these reasons, the intracellular localization and trafficking of Tß4 is still not completely defined and is still under investigation in in vivo as well as in vitro studies. In the current study we used HepG2 cells, a human hepatoma cell line; cells growing in normal conditions with fetal bovine serum expressed high levels of Tß4, restricted to the cytoplasm until 72 h. At 84 h, a diffuse Tß4 cytoplasmic immunostaining shifted to a focal perinuclear and nuclear reactivity. In the absence of serum, nuclear reactivity was localized in small granules, evenly dispersed throughout the entire nuclear envelop, and was observed as earlier as at 48 h. Cytoplasmic immunostaining for Tß4 in HepG2 cells under starvation appeared significantly lower at 48 h and decreased progressively at 72 and at 84 h. At these time points, the decrease in cytoplasmic staining was associated with a progressive increase in nuclear reactivity, suggesting a possible translocation of the peptide from the cytoplasm to the nuclear membrane. The normal immunocytochemical pattern was restored when culture cells submitted to starvation for 84 h received a new complete medium for 48 h. Mass spectrometry analysis, performed on the nuclear and cytosolic fractions of HepG2 growing with and without serum, showed that Tß4 was detectable only in the cytosolic and not in the intranuclear fraction. These data suggest that Tß4 is able to translocate from different cytoplasmic domains to the nuclear membrane and back, based on different stress conditions within the cell. The punctuate pattern of nuclear Tß4 immunostaining associated with Tß4 absence in the nucleoplasm suggest that this peptide might be localized in the nuclear pores, where it could regulate the pore permeability.

Top-down HPLC-ESI-MS detection of S-glutathionylated and S-cysteinylated derivatives of cystatin B and its 1-53 and 54-98 fragments in whole saliva of human preterm newborns.

Analysis by a HPLC-ESI-MS top-down proteomic platform of specimens of human preterm newborn whole saliva evidenced high relative amounts of cystatin B and its S-glutathionylated,S-cysteinylated, and S-S 2-mer (on Cys(3)) derivatives, decreasing as a function of postconceptional age (PCA). The percentage of S-unmodified cystatin B was higher than the S-modified isoforms in the early PCA period, differently from adults where cystatin B was detectable only as S-modified derivatives. The percentage of S-modified derivatives increased as a function of PCA, reaching at the normal term of delivery values similar to those determined in at-term newborns, babies, and adults. Moreover, in the early PCA period, high relative amounts of the 1-53 and 54-98 cystatin B fragments were detected, decreasing as a function of PCA and disappearing at the normal term of delivery. In agreement with intact cystatin B, fragment 1-53 was detectable as S-unmodified and S-modified derivatives, and their percentages changed accordingly with the percentages of intact proteins, suggesting that the fragmentation process could be subsequent to and independent from the S-modification of the protein. This study highlights specific enzymatic activity in the oral cavity of preterm newborns not present in at-term newborns and adults, which can be a clue to specialized pathways occurring during fetal oral development.

The meaning of aluminium exposure on human health and aluminium-related diseases.

The aim of this review is to attempt to answer extremely important questions related to aluminium-related diseases. Starting from an overview on the main sources of aluminium exposure in everyday life, the principal aspects of aluminium metabolism in humans have been taken into consideration in an attempt to enlighten the main metabolic pathways utilised by trivalent metal ions in different organs. The second part of this review is focused on the available evidence concerning the pathogenetic consequences of aluminium overload in human health, with particular attention to its putative role in bone and neurodegenerative human diseases.

CINtec PLUS immunocytochemistry as a tool for the cytologic diagnosis of glandular lesions of the cervix uteri.

Cytologic findings of glandular lesions of the cervix uteri are often difficult to evaluate. We studied the usefulness of CINtec PLUS p16/Ki-67 double stain (mtm laboratories, Heidelberg, Germany) for the diagnosis of glandular lesions. The study included 47 abnormal results on liquid-based cytologic tests with a subsequent histologic diagnosis of adenocarcinoma in situ or with early invasion, and 16 samples with negative results on follow-up. All samples were stained with CINtec PLUS p16/Ki-67 double stain. Of the neoplastic samples, 7 were excluded because of insufficient residual cellularity or loss of neoplastic cells. Of the samples that were adequate, 92.5% were stained with CINtec PLUS, whereas 7.5% were judged inconclusive. All inconclusive cases were at least 3 years old. Of the 16 negative samples, 15 (93.8%) stained negative and only 1 (6.2%) showed several positive clusters of cells. Our study shows that CINtec PLUS is a robust and useful tool for the diagnosis of glandular lesions of the cervix uteri.

Thymosin ß4 expression reveals intriguing similarities between fetal and cancer cells.

Thymosin ß4 (Tß4) is highly expressed in saliva of human newborns but not in adults. Here preliminary immunohistochemical analyses on different human tissues are reported. Immunoreactivity for Tß4 in human salivary glands show high quantities of Tß4 before birth, followed by downregulation of expression in adulthood. In contrast, Tß4 is detected in tumors of salivary glands, suggesting that tumor cells might utilize fetal programs, including Tß4 synthesis. Immunohistochemical analyses in the gastrointestinal tract showed strong reactivity for Tß4 in enterocytes during development, but weak immunostaining in mature enterocytes. In colorectal cancer, the association of a high expression of Tß4 with epithelial-mesenchymal transition was observed. On the basis of these data, the process of epithelial-mesenchymal transition could represent the unifying process that explains the role of Tß4 during fetal development and in cancer progression.