Synchronous "skip" facial metastases from colorectal adenocarcinoma: a case report and review of literature.

BACKGROUND: Skin metastases from colorectal adenocarcinoma are rare conditions that are metachronous in most of cases and may represent the first sign of a recurrence. These lesions are usually located to the abdominal wall on postoperative scars, perineum and chest due to direct spread from the tumor or to the lymphatic and venous dissemination. We describe a rare case of synchronous skin metastases in a patient affected by sigmoid adenocarcinoma with no sign of liver and lung repetitive lesions. CASE PRESENTATION: We admitted a 59 years old male, with no relevant medical history. He was evaluated by our tertiary center of colorectal surgery complaining diarrhoea and abdominal pain. The physical examination revealed a palpable mass in left flank of the abdomen. The colonoscopy showed a sub-stenosis of the sigmoid colon (G2 adenocarcinoma). No repetitive lesions were detected by the preoperative CT scan. The patient reported a rapid grow of a soft supralabial and chin nodules in the last 2 months, which he believed to be related to the use of the mask due to COVID-19 pandemic. A laparoscopic left hemicolectomy with complete mesocolic excision and a local excision of both facial nodules were performed. The histological examination revealed a poorly differentiated signet ring cell colorectal adenocarcinoma with metastases in seven pericolic lymphonodes. The excisional biopsy of the skin nodules revealed a subcutaneous metastases from primary colorectal tumour. CONCLUSIONS: As far as we know, synchronous facial metastases from colorectal cancer in the absence of any other metastases has never been described before. The onset of new skin nodules in patients affected by colorectal cancer should raise-up the clinical suspicion of metastatic lesions even when repetitive lesions are not detected in the liver or lungs.

The role of PIAS3, p-STAT3 and ALR in colorectal cancer: new translational molecular features for an old disease.

OBJECTIVE: Human colorectal cancer (CRC) is characterized by a sequence of biological events that determine its induction and progression. Gut microbiota has an important role in this multistep model of carcinogenesis, as well as constitutive activation of Signal Transducer and Activator Factors 3 (p-STAT3) and Protein Inhibitor of Activated STAT3 (PIAS3), which negatively controls STAT3. It has been reported that a liver growth factor, the Augmenter of Liver Regeneration (ALR), an anti-apoptotic, anti-metastatic factor, exerts protective/cell survival and anti-metastatic activities and has been detected highly expressed in neoplastic cells. PATIENTS AND METHODS: To evaluate, by immunohistochemistry, p-STAT3, PIAS3 and ALR expression in neoplastic human tissues from CRC patients, grouping the data in accordance with the histological alterations (G1, G2 and G3) and metastasis presence. Western blot (WB) analysis of ALR was also determined in neoplastic and surrounding tissues. Finally, cell proliferation (Ki-67) and apoptosis (Bcl-2) were determined. RESULTS: Colon cancer tissue samples showed: (1) ALR and p-STAT3 strongly over-expression in 100% of G1 tissue samples, reducing in G2 and G3 tissue samples; (2) PIAS3 immunological determination was poorly expressed in G1 tissue samples and highly expressed in the 100% of colorectal tissues from group G2 and G3. Ki-67 progressively increases with the importance of the anatomic-pathological alterations and Bcl-2 resulted higher in G3 tissue samples compared to G1 neoplastic tissues. WB data evidenced, in neoplastic tissues, compared to the tumour-surrounding tissues, ALR over-expressed in G1 neoplastic tissues and down-expressed in G3 neoplastic tissues. CONCLUSIONS: Our data demonstrate a different dynamism of the investigated factors in relation to the severity of CRC histological findings. We hypothesize that the positive expression of ALR and p-STAT3 in the neoplastic tissue samples from CRC G1 group, associated to the absence of PIAS3, could be useful marker to identify an early stage of the disease. Based on these data and on our previous studies on gut microbiota in precancerous intestinal lesions, we are confident that, after microbial priming, a cascade of molecular events is started. So, the detectable molecules acting in these initial steps should be considered for the study of CRC progression and therapy.

Direct access in physical therapy: a systematic review.

BACKGROUND: Grooving evidence suggests that patients could have Direct Access (DA) to physiotherapy. It represents a new model of care, which might lead to improve patients' health status and decrease cost services for healthcare compared with a secondary care referral pathway. The aim of this study is to explore the evidence regarding feasibility, effectiveness, costs, safety and patient satisfaction through DA compared to other organizational models. METHODS: A systematic review was carried out through MEDLINE, CINAHL, and EMBASE databases from their inceptions until March 2018 using keywords related with DA. All articles in English, Italian or Polish comparing the modality of DA with any other organizational modality were included. Two reviewers independently selected eligible studies, extracted the data, and assessed methodological quality using the Newcastle-Ottawa Scale for cohort studies. RESULTS: 1593 articles were initially identified, and thirteen studies met the inclusion criteria. The mean NOS score for study quality was 6.4 ± 1.4 out of a possible total score of nine points. Patients impairments and health care status, were similar through all studies. DA showed less number of physiotherapy treatments, visits to physician, imaging performed and required fewer non-steroidal anti-inflammatory drugs and secondary care. Patients were more satisfied with the service in comparison to the group referred by the physician. and costs per subject were lower. DA patients were younger, with a higher level of education; mostly, they presented a less severe clinical condition and a more acute pathologies related to the spine. No harms were reported. Only one study assessed the clinical safety of the DA. CONCLUSION: The findings suggest that DA to physiotherapy is feasible considering the clinical and economic point of view. However, more research is still needed due to the low evidence of the reviewed studies and to explore the clinical safety of DA.

Primary intestinal choriocarcinoma in a patient with long-standing Crohn's disease.

Extra-gonadal choriocarcinoma is an extremely rare highly malignant neoplasm with a poor prognosis. In the gastrointestinal tract it usually arises in stomach, esophagous, bowel intestine and colon. Only few cases are pure and not associated with a classic adenocarcinoma. The correlation of Crohn's disease with choriocarcinoma is not reported. We describe a case of 47-year old man with primary choriocarcinoma of the colon in a previously documented Crohn's disease.

Small intestinal bacterial overgrowth and celiac disease: A systematic review with pooled-data analysis.

BACKGROUND: A link between small intestinal bacterial overgrowth (SIBO) and celiac disease (CD) has been hypothesized. METHODS: Literature search was performed in main medical databases. Methods of analysis/inclusion criteria were based on Preferred Reporting Items for Systematic reviews and Meta-Analyses recommendations. The end-point was to estimate, by a pooled-data analysis, SIBO prevalence in CD. Proportions/percentages and their 95% confidence intervals (CI) were calculated by inverse variance method, whereas odd ratios (OR) and their 95% CI were estimated, where available, based on the Mantel-Haenszel method. Data were entered into the RevMan 5.3 software. KEY RESULTS: Eleven articles fulfilled considered criteria. The pooled mean prevalence of SIBO in CD was 20% (95% CI of 10%-30%). In comparison to asymptomatic controls, CD was associated to higher risk of SIBO, with an OR of 10.52 (95% CI 2.69-41.21, P=.0007). Jejunal aspirate culture assessed SIBO prevalence of 11% (95% CI 3%-19%) in CD, whereas breath tests detected a higher value (23%, 95% CI 10%-37%). The pooled prevalence of SIBO in CD patients who were symptomatic despite a GFD was 28% (95% CI 10%-47%), higher than in asymptomatic celiac patients (pooled prevalence of 10%, with a 95% CI of 3%-16%), despite not statistically significant (P=.06). When GFD-unresponsive CD was defined only by clinical persistence of symptoms, the prevalence of SIBO was higher than in the case of villous atrophy association (31% vs 16% P=.33). CONCLUSIONS: The heterogeneity of available studies may not support a relationship SIBO-CD. Nevertheless, SIBO could be more common in CD when symptoms do not improve after GFD.

Small bowel obstruction caused by Anisakis and Meckel's diverticulum: a rare case.

INTRODUCTION: Anisakiasis is a parasitic infection caused by the ingestion of raw fish contaminated by larval nematodes of Anisakis species. Intestinal or extraintestinal manifestations are rated to > 4% and >1% respectively. PRESENTATION OF CASE: A 61-year old patient was admitted to our General Surgical and Emergency Unit because of sudden abdominal pain, vomit and constipation. He had eaten raw fish 3 days before admission. Laboratory data showed high levels of WBC and PCR. CT scanning showed "dilation of jejunum and ileum loops, thickening of the terminal ileum and cecum and signs of inflammation of the intestinal wall and mesentery". The following emergency surgical procedure was performed: laparotomy with evidence of obstruction of the small bowels, a giant Meckel's diverticulum, resection of terminal ileum and cecum and ileocolonic anastomosis. At the microscopic examination, the intestinal wall appeared occupied by a transmural inflammatory infiltrate, mainly eosinophilic, edema and nematode larvae, referable to Anisakis, surrounded by necrotic-inflammatory material. Moreover, there was evidence of giant a Meckel's diverticulum. DISCUSSION: Normally, enteric anisakiasis exhibits leukocytosis with eosinophilia and high CRP levels. There are cases of successful medical treatment and other cases of endoscopic treatment avoiding surgical procedure. In our case, enteric Anisakias had not been taken into consideration at the moment of the operation and only histopathology could reveal Anisakis larvae inside the intestinal wall. CONCLUSION: Our surgical approach is considered in literature as the best one for this clinical presentation. Those patients need to be better studied and more attention should be paid to their history.

Disseminated tumour cells in bone marrow in experimental colon cancer: metastatic or resident?

AIM: There are conflicting data on the biological and prognostic significance of disseminated tumour cells (DTCs) in the bone marrow of colorectal cancer patients since bone metastasis is rare in this disease. The study aimed to determine the origin of bone marrow DTCs using human colorectal cancer cells in in vivo and in vitro experimental settings. METHOD: CD1 nude female mice were xenotransplanted with SW620 cells (a colorectal cancer cell line isolated from a male patient) injected in the colon wall. At autopsy, the presence of SW620 in the bone marrow (BM), colon and other organs/tissues was recognized by detection of the epithelial marker cytokeratin-19 (CK19) and Y chromosome. In addition SW620 cells or their conditioned medium were cultured with human BM cells. RESULTS: Macroscopically evident CK19+/Y-chromosome-positive tumours developed only in five mice receiving SW620 cells while putative DTCs (CK19+) were found in the bone marrow of all treated mice. Most of these CK19+ cells were Y chromosome negative, only few being Y chromosome positive. In vitro SW620 cells or their conditioned medium induced CK19 expression in cultured human bone marrow cells. CONCLUSION: Experimental colorectal cancer can induce the appearance of two distinct CK19+ cell populations in the bone marrow, one of metastatic origin and the other of murine origin. These findings suggest that bone marrow cells may undergo phenotypic modifications induced by cancer cells.

Colonic lipomas. Three surgical techniques for three different clinical cases.

Colonic lipomas larger than 2 cm in diameter are likely to be symptomatic. In some cases a complication is the first clinical sign. Massive lower intestinal bleeding or obstruction, acute bleeding, prolapse or perforation or, rarely, acute intussusception with intestinal obstruction require urgent surgery. Diagnosis is often made following colonoscopy, which can also have a therapeutic role. Imaging procedures such as CT has a secondary role. Patients with small asymptomatic colonic lipomas need regular follow up. For larger (diameter > 2 cm) and/or symptomatic lipomas, resection should be considered, although the choice between endoscopic or surgical resection remains controversial. We believe that even lipomas > 2 cm can safely be removed by endoscopic resection. If surgery is indicated, we consider laparoscopy to be the ideal approach in all patients for whom minimally invasive surgery is not contraindicated.

Orbital granular cell tumor in a patient with Churg Strauss syndrome: the importance of biopsy.

A 65-year-old woman presented with a long standing, progressive exophthalmos of the right eye. Her medical history was significant for Churg Strauss syndrome, and was treated with immunosuppressive therapy. She had undergone two previous orbital biopsies showing inflammatory reactive lymphoid hyperplasia. A diagnosis of orbital inflammation in Churg-Strauss syndrome was suspected, and the immunosuppressive therapy was increased. Because of the lack of response to therapy, a further biopsy was performed, by lateral orbitotomy approach. Biopsy of the mass revealed a granular cell tumor composed of S-100 positive cells with an acidophilic granular cytoplasm and peripheral lymphocytic infiltration. A granular cell tumor, which is very rare in the orbit, should be considered in the differential diagnosis of orbital tumors, and if suspected, an excisional biopsy must be undertaken. Typical histopathological aspect of the granular cell tumor is characterized by the presence of S-100 positive closely packed polygonal cells with a granular cytoplasm.

Protection of intestinal anastomosis with biological glues: an experimental randomized controlled trial.

BACKGROUND: The aim of the study was to compare the degree of healing and air tightness of hand-sewn colonic anastomoses provided by different biological glues. METHODS: Thirty colonic anastomoses were fashioned in ten rabbits, at 5, 10, 15 cm from the ileocecal valve, with 4/0 PDS running sutures. Each suture was randomized to treatment with fibrin sealant (Tissucol®), a synthetic glue (Coseal®), or nothing (control). After 15 days, the rabbits were killed and the anastomoses examined for their integrity and resistance to bursting. The van der Hamm scale was used to evaluate postoperative adhesions. A blind histological evaluation of the newly formed tissue was made (Ehrlich-Hunt scale). RESULTS: Two rabbits developed an intraabdominal abscess, one in the control anastomosis group without glue. Postoperative adhesions were present in all animals. Median anastomosis bursting pressures were 0.9 atm in all three groups: Tissucol, Coseal, and control. Pressure values were 0.9, 1.0, and 0.9 atm in the three different proximodistal sites, respectively. A trend toward an increased resistance was observed in the glued anastomosis, although this was not significant. Lymphocyte infiltration, fibroblast activity, blood vessel density, and collagen deposition were lower in controls. Anastomoses treated with Tissucol had the highest lymphocyte infiltration level. The Coseal group developed the highest rates of fibroblast activity, collagen deposition, and blood vessel neogenesis. CONCLUSION: The use of biological glues did not result in a statistically significantly increased bursting resistance. Histological evaluation demonstrated more intense tissue neoformation in the glue groups, particularly in the Coseal group. The role of biological glues in decreasing the leakage rate of intestinal anastomoses is uncertain, and larger trials using different protective agents are warranted.

Hepatocellular Carcinoma Metastasis to the Orbit in a Coinfected HIV+ HBV+ Patient Previously Treated with Orthotopic Liver Transplantation: A Case Report.

Hepatocellular carcinoma rarely metastasizes to the orbit. We report a 45-year-old male, HBV+, HIV+, with a past history of a liver transplant for ELSD (end-stage liver disease) with hepatocellular carcinoma and recurrent HCC, who presented with proptosis and diplopia of the left eye. CT scans of the head revealed a large, irregular mass in the left orbit causing superior and lateral destruction of the orbital bone. Biopsy specimens of the orbital tumor showed features of metastatic foci of hepatocellular carcinoma. Only 16 other cases of HCC metastasis to the orbit have been described in literature, and this is the first case in a previously transplanted HIV+, HBV+ patient.

Abdominal nodal localization of Castleman's disease: report of a case.

INTRODUCTION: Castleman's disease (CD) is a rare benign disorder that may grow in any area where lymphoid tissue is normally present but the most frequent site is mediastinum (67%); the abdomen is rarely affected by this pathology. In the pathogenesis of CD an important role could be played by HHV-8. Diagnosis is difficult and the diagnostic certainty is obtained only by histological examination. For this disease there is no gold-standard treatment. CASE REPORT: We report the case of a woman of 33 years of age affected by a rare form of abdominal nodal localization of Castleman's Disease for which the patient underwent surgery. CONCLUSION: CD must be included in the differential diagnosis of retroperitoneal tumors even though the definitive diagnosis can only be achieved by histological and immunohistochemical examination. In the case of single location, the treatment of choice is surgical removal.

ER-beta expression in large bowel adenomas: implications in colon carcinogenesis.

BACKGROUND: A pivotal role of oestrogen receptor-beta has been suggested in colon carcinogenesis in humans. However, few data are available on oestrogen receptor-beta in colorectal pre-cancerous lesions. AIM: In the present study, we evaluated oestrogen receptor-beta expression and its possible correlation with proliferative activity and apoptosis in colorectal adenomas and normal colon tissue. PATIENTS/METHODS: Adenomatous tissue from 25 patients with colonic polyps, and normal tissue from 25 controls were used. Oestrogen receptor-beta expression, colonocyte proliferation (expressed as PCNA positivity) and apoptosis were evaluated. RESULTS: In adenomatous tissue, a significant reduction of oestrogen receptor-beta was observed compared to normal mucosa (10.1+/-5.5% vs. 44.2+/-13.7; p<0.03), while the expression of oestrogen receptor-alpha remained unvaried. Cell proliferative activity significantly increased in adenomatous tissue compared to normal mucosa (59.3+/-7.1 vs. 18.5+/-8.8; p<0.0001), doubling the PCNA/apoptosis ratio. An inverse correlation was found between oestrogen receptor-beta and PCNA expression in adenomas (r=-0.81), a datum confirmed by confocal microscopy evaluation. CONCLUSIONS: Our data demonstrate, for the first time, a significant reduction of oestrogen receptor-beta expression already in the pre-cancerous phase of colon carcinogenesis. This suggests a role of selective oestrogen receptor-beta agonists in the prevention of colorectal cancer.

Primary localized orbital amyloidosis: a case report.

PURPOSE: Amyloidosis refers to a heterogeneous group of disorders associated with deposition of chemically distinct fibril proteins. Isolated orbital amyloidosis is a rare condition and requires systemic examination. The authors report a case of amyloid deposit in the orbit whose systemic investigation has been negative. METHODS: A 64-year-old woman presented to the eye clinic with left-sided orbital mass, mild exophthalmos with downward ocular displacement, and ptosis. The patient presented also visual acuity loss and ocular hypertension. No systemic involvement was noted by systemic workup and it confirmed the primary orbital amyloidosis. RESULTS: The patient was subject to full clinical examination, laboratory examinations, orbital echography, magnetic resonance imaging and total body computed tomography scans, rectal mucosa, and temporal artery biopsies. It was necessary to exclude systemic amyloidosis. The presence of amyloid deposits was confirmed by biopsy of orbital mass. The chemical nature of deposit was characterized using light microscopy, immunohistochemistry, and electron microscopy. CONCLUSIONS: Orbital amyloidosis is a very rare disease. It should be considered in the diagnosis of patients with ptosis and exophthalmos. The treatment usually consists of surgical removal of the amyloid mass and follow-up for a likely local recurrence. In our case, mass excision determined the decrease of exophthalmos and intraocular pressure.

Confocal laser scanning microscope study of terminal villi vessels in normal term and pre-eclamptic placentas.

The aim of this study was to compare immunocytochemical confocal scanning laser microscopy measures of villus capillarization in control placentas with pre-eclamptic ones. Accordingly, placentas from normal term pregnancies (n=3) and cases of late-onset pre-eclampsia without intrauterine growth retardation (IUGR) featuring normal uterine artery Doppler (n=3) were analyzed by confocal scanning laser microscopy (CSLM), which is a powerful technique for obtaining three-dimensional reconstructions of any kind of blood vessels (arteries, veins, capillaries). A laser light beam is used in order to detect CD34 antibody-related immunofluorescence, which is a marker of endothelial cells. Villus capillarization was assessed by estimating the following parameters: number of pixels, mean, maximum and minimum immunofluorescence amplitude. Our results show a significant hyper-ramification of the capillary loop in pre-eclamptic placentas, featuring irregular profile and narrow lumina. Such findings support the hypothesis that several agents causing angiogenesis and vasoconstriction affect villus vessels in pre-eclamptic placentas, thus promoting a lasting condition of fetal hypoxia by decreasing endothelial surface and materno-fetal exchanges.

[Unusual presentation of metastatic osteosarcoma as a giant duodenal polyp. A case report]. / Osteosarcoma metastatico polipoide del duodeno. descrizione di un caso ad insolita presentazione.

INTRODUCTION: Osteosarcoma is a malignant bone neoplasm with an usually high metastatic potential. Besides the common metastatic sites such as lungs, bone, and pleura, metastases to unusual sites such as liver, brain and regional lymph nodes have also been reported with increasing frequency; among them, gastrointestinal metastases represent an extraordinarily rare event in the natural history of this neoplasia. MATERIALS AND METHODS: We describe a case of a 27 year old man, who was diagnosed with a grade IV osteoblastic osteosarcoma of the left tibia and submitted to 5 courses of pre-surgical chemotherapy; later he underwent tibial resection with implantation of a prosthesis, followed by 2 further courses of adjuvant chemotherapy. Five years after the patient presented with melena and acute anemia; during endoscopic examination, a large bleeding duodenal polyp was found, so a surgical resection of the gastric antrum, duodenum, head of the pancreas, main bile ducts and gallbladder was performed. The surgical specimen was formalin fixed and paraffin embedded, and sections obtained by the blocks were stained with haematoxylin-eosin; immunohistochemical and ultrastructural analysis were performed. RESULTS: Microscopically, the tumor mass showed a mostly fasciculated architecture, composed of spindle and epithelioid cells in a scarce fibromyxoid stroma, featuring large areas of coagulative necrosis and small foci of sclerohyalinosis. Tumor cells featured large vesciculous nuclei, with a few prominent nucleoli; no foci of osteoid matrix were detectable. The ultrastructural analysis revealed small calcified electron-dense depots both in the perinuclear cytoplasm and in the extracellular collagen matrix compatible with an "early osteoid formation". Due to alteration of the natural history of the tumor induced by multiagent chemotherapy, the rate of metastases of osteosarcoma to unusual sites has been increasing. We report the 9th case of a gastrointestinal metastasis of osteosarcoma reported thus far, and only the second one arising in the duodenum. Both the histological features and the immunohistochemical findings were not suggestive for osteosarcoma metastases because the tumor appeared dedifferentiated; in our case the combination of electron microscopy and clinical history played a pivotal role to establish the final diagnosis.