Optimization of an Ex-Vivo Human Skin/Vein Model for Long-Term Wound Healing Studies: Ground Preparatory Activities for the 'Suture in Space' Experiment Onboard the International Space Station.

This study is preliminary to an experiment to be performed onboard the International Space Station (ISS) and on Earth to investigate how low gravity influences the healing of sutured human skin and vein wounds. Its objective was to ascertain whether these tissue explants could be maintained to be viable ex vivo for long periods of time, mimicking the experimental conditions onboard the ISS. We developed an automated tissue culture chamber, reproducing and monitoring the physiological tensile forces over time, and a culture medium enriched with serelaxin (60 ng/mL) and (Zn(PipNONO)Cl) (28 ng/mL), known to extend viability of explanted organs for transplantation. The results show that the human skin and vein specimens remained viable for more than 4 weeks, with no substantial signs of damage in their tissues and cells. As a further clue about cell viability, some typical events associated with wound repair were observed in the tissue areas close to the wound, namely remodeling of collagen fibers in the papillary dermis and of elastic fibers in the vein wall, proliferation of keratinocyte stem cells, and expression of the endothelial functional markers eNOS and FGF-2. These findings validate the suitability of this new ex vivo organ culture system for wound healing studies, not only for the scheduled space experiment but also for applications on Earth, such as drug discovery purposes.

Surgery in the Next Space Missions.

In the coming years, missions to the Moon and Mars shall be the new goals of space flight. The complexity of these missions due to the great distance from Earth and the unforeseen obstacles to settle on another planet have given rise to great concerns for crew health and survival. The need for advanced crew autonomy and a different approach to surgical emergency require new protocols and devices to help future crew medical officers and other crew members in a task of unprecedented difficulty. Hence, the increasing variety of schedules, devices, and protocols being developed. A serious health problem, such as an emerging surgical disease or severe trauma, can jeopardize the mission and survival of the entire crew. Many other difficulties are present in deep-space missions or settlements on other planets, such as communication and supply, also medical, delays, and shortage, and the presence of radiation. Progress in advanced technologies as well as the evolution of robotic surgery and the use of artificial intelligence are other topics of this review. In this particular area of research, even if we are still very far from an "intelligent robot", this evolution must be evaluated in the light of legislative and ethical considerations. This topic was presented at the annual meeting of the American College of Surgeons-Italy Chapter in 2021.

Exploitation of Skin Microbiota in Wound Healing: Perspectives During Space Missions.

Wound healing is slowed in Space. Microgravity and possible physical factors associated with Space affect alterations in fibroblast, matrix formation, dysregulation in apoptosis and inflammation. The microbial populations settled on skin, space modules, in space suits, are also playing a pivotal role, as wound healing is also affected by the microbial community. We propose a perspective that includes four domines for the application of human skin microbiota for wound healing in Space: The natural antimicrobial properties of the skin microbiota, the crosstalk of the skin microbiota with the immune system during wound healing, the contribution of the microbiota in precision medicine, and the role of gut-skin and gut-brain axes. A stronger understanding of the connections and metabolic network among bacteria, fungi, the host's immune system and the host metabolism will support the basis for a better wound healing in Space.

Laparosacopic management with combination of fatty meal and methylen-blu for chylous leak after a left para-aortic paraganglioma excision.

We report a case of chylous leak recognized post-operatively after abdominal surgery for left para-aortic paraganglioma in a young female with a history of open botallo's duct. Conservative measures failed to control the leak and the patient is not eligible for sclerotisation. Laparoscopic exploration with intralipidand methylen blue injection through an orogastric tube revealed the leaking area near the superior mesenteric vein behind the Traitz, and this was ligated with non-asorbable suture and placement of acrylic glue. The patient was discharged the 7th post-operative day after removal of the drainage which appeared to supply <100 cc of serum material. Outpatient control was successful and the patient is actually in good conditions.

Multispectral imaging autofluorescence microscopy in colonic and gastric cancer metastatic lymph nodes.

BACKGROUND & AIMS: The lymphadenectomy and extended lymphadenectomy procedures have been points of controversy in surgical oncology. The methods available for the detection of metastatic lymph nodes are numerous. These include lymphoscintigraphy and radiolabeled antibody detection, but in most cancers the currently used technique is sentinel lymph node identification, performed primarily through the use of immunohistochemistry. We propose the application of autofluorescence (AF)-based techniques for lymph node evaluation in colorectal and gastric tumors. METHODS: We studied 30 clinical cases: 15 colorectal cancers and 15 gastric cancers. All of the patients were in the advanced stages of the disease and were candidates for adjuvant therapy. Autofluorescence microspectroscopy and multispectral imaging autofluorescence microscopy have been used to analyze the AF emission of metastatic lymph node sections, excited with 365-nm wavelength radiation. The AF spectra were recorded in the range of 400-700 nm. Monochrome AF images were acquired sequentially through interference filters peaked at 450, 550, and 650 nm, and then combined together in a single red-green-blue image. The AF pattern and the emission spectrum of metastatic lymph nodes have unique characteristics that can be used to distinguish them from the normal ones. RESULTS: The results, compared with standard histopathologic procedures and with specific staining methods, supplied a satisfactory validation of the proposed technique, revealing the possibility of improving the actual diagnostic procedures for malignant lymph node alterations. CONCLUSIONS: With the development of appropriate instrumentation, the proposed technique could be particularly suitable in intrasurgical diagnosis of metastatic lymph nodes.

Peripheral paraneoplastic neuropathy, an uncommon clinical onset of sigmoid cancer. Case report and review of the literature.

A case of a 76-year-old man presenting with weakness of the lower legs and bilateral steppage gait is described. Neurological examination revealed a sensorimotor neuropathy with axonopathy and myelinic aspects. At the time of the diagnostic workup an episode of rectal bleeding occurred. Colonoscopy demonstrated an exophytic cancer of the sigmoid colon at 40 cm from the anal verge. At surgery the tumor adhered to the ileum, so a left hemicolectomy and ileo-ileal resection were performed. Tumor stage was Dukes' B, Jass III, Astler-Coller B2, T3N0M0. The patient underwent postoperative chemotherapy and was followed for the past three years. At present he is free of disease and the neuropathy has completely regressed without any dedicated therapy. As reported in the literature the appearance of a paraneoplastic neurological syndrome (PNS) may be the first sign of a malignancy that is occult at the time of clinical presentation. The most widely supported theory about its etiology is that of an autoimmune origin. The paraneoplastic neurological syndrome is considered to be at a point of intersection between tumor immunology, autoimmune neurological disease, and basic neurobiology. Previous experience has resulted in a pathogenic model and in a definition of a group of autoantibodies related to the disease. Small cell lung cancer (SCLC) is the neoplasm most frequently associated with PNS; other malignancies include lymphomas and various hematological malignancies. Some authors reported also that the percentage of patients with a high titer of neuronal autoantibodies is small and several of the autoantibodies are present at low levels without any accompanying clinical manifestation. In a clinical retrospective study of the Mayo Clinic Group 115,081 patients were examined over the period 1984-1993 and only 58 patients (0.05%) could be defined as being affected by a paraneoplastic neurological syndrome. Only five of these patients had colon tumors. The number of patients is so small and so widely scattered among publications that no statistical analysis is possible. Probably the only possibility for early identification of such a syndrome is a high degree of suspicion. In fact, these patients are usually first admitted and studied in a neurological unit, and the diagnosis of a tumor-associated disease is a delayed event.

Multimodal imaging in the diagnosis and evaluation of intestinal malrotations in adults: a case report.

Midgut malrotation is a congenital anomaly referring to either lack of or incomplete rotation of the fetal intestines around the axis of the superior mesenteric artery during fetal development. It is rare in adulthood and the true incidence is difficult to estimate because most patients are asymptomatic. The diagnosis is usually performed with several radiological and surgical methods. We report a case of a woman who presented with cramp-like abdominal pain localized to the right iliac fossa. The patient underwent abdominal ultrasound, radiological examination without and with contrast, and computed tomography with three-dimensional volume rendering reconstruction. Although small bowel followthrough is often enough to recognize the type of malrotation, using multimodal imaging may offer a better definition of this abnormality with a better definition of the kind of malrotation, by adding additional anatomical information. In our case, the imaging clearly showed malrotation of the small bowel with reverse rotation of the colon. Hence a multimodal imaging strategy proved useful for the diagnosis of intestinal malrotation in an adult afflicted by chronic cramp-like abdominal pain.

Role of conventional treatments on circulating and monocyte-derived dendritic cells in colorectal cancer.

We investigated the effects of metastasis, surgery and chemotherapy on both circulating dendritic cells (DCs) and monocyte-derived-DCs (MoDCs) in colorectal cancer (CRC) patients. Metastatic or nonmetastatic CRC patients had significantly reduced DC subsets compared to healthy subjects (p < 0.001). These cells were significantly higher in metastatic than in nonmetastatic patients. MoDCs were significantly lower in metastatic than healthy and nonmetastatic subjects (p < 0.001). Surgically treated patients had nearly one-half circulating DC subsets compared to healthy subjects (p < 0.001) while no difference was found between unoperated and healthy subjects. MoDCs obtained from tumor-bearing were significantly higher than in operated subjects. In both cases, MoDCs were significantly lower than in healthy subjects (p < 0.001). Circulating DCs and MoDCs were significantly lower in CRC patients, with or without chemotherapy, compared to healthy subjects (p < 0.001). Compared to untreated, chemotherapy-treated patients had 30% fewer DC subsets and lower MoDCs. Characterization of circulating DC subsets and MoDCs may elucidate CRC patients' immune system status.

p53 and DPC4 alterations in the bile of patients with pancreatic carcinoma.

INTRODUCTION: Pancreatic cancer is still predominantly diagnosed in advanced stages, and 85%-90% of patients are not eligible for surgery at diagnosis. This is mainly due to the great difficulty in detecting the tumour at an early stage and presently no satisfactory results have been obtained to overcome this problem. Studies on molecular genetic profile of pancreatic cancer may represent an important approach. This study was focused on the mutations of p53 and DPC4 detectable in the bile of patients with histologically proven pancreatic cancers. MATERIALS AND PATIENTS: We analysed specimens of bile collected through percutaneous transhepatic biliary catheters, placed to treat malignant biliary obstruction in 25 patients with pancreatic adenocarcinoma. A percentage of mutation was obtained of 43 % for the microsatellite D17S945 (p53), 54% and 50 % for D18S46 and D18S474 (DPC4), respectively. The percentage of amplification was 67%, 93,6%, and 80%. CONCLUSION: We consider the results encouraging enough to decide to enlarge the number of patients examined. The aim is to determine if a test for DPC4 and p53 mutations is eligible for introduction in clinical routine use. More sets of samples are required to satisfactorily answer this question.