Longitudinal, virological, and serological assessment of hospitalized COVID-19 patients.

Here we described the virological and serological assessment of 23 COVID-19 patients hospitalized and followed up in Milan, Italy, during the first wave of COVID-19 pandemic. Nasopharyngeal (NPS), anal swabs, and blood samples were collected from 23 COVID-19 patients, at hospital admission, and periodically up to discharge, for a median time of 20 days (3-83 days). RNA was isolated and tested for SARS-CoV-2 by qRT-PCR; anti-SARS-CoV-2 IgM and IgG antibody titers were evaluated in serum samples by ELISA. SARS-CoV-2 genome was detected in the NPS swabs of the 23 patients, at the admission, and 8/19 (42.1%) were still positive at the discharge. Anal swabs were positive to SARS-CoV-2 RNA detection in 20/23 (86.9%) patients; 6/19 (31.6%) were still positive at discharge. The mean time of RNA negative conversion was 17 days (4-36 days) and 33 days (4-77 days), for NPS and anal swabs, respectively. SARS-CoV-2-RNA was detected in the blood of 6/23 (26.1%) patients. Thirteen/23 (56.5%) and 17/23 (73.9%) patients were seropositive for IgM and IgG, respectively, at the admission, and the median IgM and IgG levels significantly (p < 0.05) increased after 13 days. Although the limited cohort size, our report provides evidence that SARS-CoV-2 is shed through multiple routes, with important implications in healthcare settings.

Human Endogenous Retroviruses Long Terminal Repeat Methylation, Transcription, and Protein Expression in Human Colon Cancer.

Colon cancer is the fourth most common malignancy in both incidence and mortality in developed countries. Infectious agents are among the risk factors for colon cancer. Variations in human endogenous retrovirus (HERV) transcript and protein levels are associated with several types of cancers, but few studies address HERV expression in colon cancer. Fifty-eight patients with advanced-stage colon cancer were enrolled in this study. HERV-H, -K (HML-2), -P LTRs, Alu, and LINE-1 methylation levels and transcription of HERV-H, -K (HML-2), and -P env and HERV-K pol genes in normal adjacent and tumor tissues were investigated by pyrosequencing and RT-qPCR, respectively. Expression of the HERV-K (HML-2) Pol and Env proteins in selected tissues was examined by Western blotting. Associations between HERV transcript expression and methylation levels and between clinical characteristics and HERV expression were evaluated. Compared to adjacent normal tissues, LINE-1 was hypomethylated in tumor tissues (p < 0.05), whereas Alu, HERV-K (HML-2), and -H LTRs showed a decreasing trend in tumor tissue compared to normal tissue, though without a significant difference. The transcription levels of HERV env and pol genes were similar. However, the HERV-K (HML-2) Pol protein was more highly expressed (p < 0.01) in surrounding normal tissues, but the HERV-K (HML-2) Env protein was only expressed in tumor tissues. Although HERV LTR methylation and gene expression did not show significant differences between tumor and normal tissues, HERV protein expression differed greatly. Pol protein expression in normal cells may induce reverse transcription and subsequent integration into the host genome, likely favoring cell transformation; in contrast, the Env protein in tumor tissue may contribute to cancer progression through cell-to-cell fusion.

Management of surgical working in an Italian neighborhood hospital during the COVID-19 pandemic.

The novel SARS-CoV-2 pandemic arose in China in the late 2019 and soon after spread in the rest of the world. The management of SARS-CoV-2 is a serious challenge for all the healthcare professionals. The management of this disease has caused an epochal change in all of the hospitals. The surgical departments too were not excluded from management of COVID-19 patients, because of the disease itself, or as complication of surgical procedure. The surgeons too had to quickly adapt their skills, in order to recognize and treat this life-threatening problem. In the meantime, the surgeons had to ensure continuity of the oncall availability for the emergency procedures, meanwhile the regular scheduled surgical activities were suspended. We present here our experience in a neighborhood hospital located in Milan, Italy.

GNAS mutations as prognostic biomarker in patients with relapsed peritoneal pseudomyxoma receiving metronomic capecitabine and bevacizumab: a clinical and translational study.

BACKGROUND: There is lack of evidence about systemic treatment of pseudomyxoma peritonei (PMP) relapsing after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. There is also lack of biomarkers able to predict outcomes beyond known clinical and pathological prognostic features. METHODS: Fifteen patients with relapsed PMP and progressive disease within the last 6 months were included and received metronomic capecitabine (625 mg/mq/day b.i.d.) and bevacizumab (7.5 mg/Kg three-weekly) until progressive disease/unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Ion Torrent(®) next generation sequencing technology (Hot-spot Cancer Panel) was used to characterize molecular features. RESULTS: At a median follow up of 12 months, median PFS was 8.2 months and 1-year overall survival was 91 %. Partial responses were observed in 20 % of cases, but a significant reduction of tumor markers in up to 79 %. Treatment was very well tolerated without no new safety signals. All tumor samples except one had KRAS mutations. Patients with GNAS mutations had a significantly shorter median PFS as compared to GNAS wild-type ones (5.3 months vs. not reached; p < 0.007). The results were externally validated on our previous series of PMP patients. GNAS mutations were rare in a parallel cohort of 121 advanced colorectal cancers (2.5 %), but were associated with peculiar clinical-pathological features and aggressive course. CONCLUSIONS: Metronomic capecitabine and bevacizumab is an active and well tolerated option in patients with relapsed PMP. The negative prognostic effect of GNAS mutations in gastrointestinal cancers warrants further confirmatory studies and may prompt the development of effective targeted strategies.

Peritonectomy and hyperthermic intraperitoneal chemotherapy: cost analysis and sustainability.

BACKGROUND: Malignancies of the peritoneum remain a challenge in any hospital that accepts to manage them, due not only to difficulties associated with the complexity of the procedures involved but also the costs, which - in Italy and other countries that use a diagnosis-related group (DRG) system - are not adequately reimbursed. MATERIAL AND METHODS: We analyzed data relative to 24 patients operated on between September 2010 and May 2013 with special regard to operating room expenditure, ICU stay, duration of hospitalization, and DRG reimbursement. The total costs per patient included clinical, operating room, procedure, pathology, imaging, ward care, allied healthcare, pharmaceutical, and ICU costs. RESULTS: Postoperative hospital stay, drugs and materials, and operating room occupancy were the main factors affecting the expenditure for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. We had a median hospitalization of 14 days, median ICU stay of 2.4 days, and median operating room occupancy of 585 min. The median expenditure for each case was € 21,744; the median reimbursement by the national health system € 8,375. CONCLUSIONS: In a DRG reimbursement system, the economic effort in the management of patients undergoing peritonectomy procedures may not be counterbalanced by adequate reimbursement. Joint efforts between medical and administration parties are mandatory to develop appropriate treatment protocols and keep down the costs.

Introducing an enhanced recovery after surgery program in colorectal surgery: a single center experience.

AIM: To study the implementation of an enhanced recovery after surgery (ERAS) program at a large University Hospital from "pilot study" to "standard of care". METHODS: The study was designed as a prospective single centre cohort study. A prospective evaluation of compliance to a protocol based on full application of all ERAS principles, through the progressive steps of its implementation, was performed. Results achieved in the initial pilot study conducted by a dedicated team (n = 47) were compared to those achieved in the shared protocol phase (n = 143) three years later. Outcomes were length of postoperative hospital stay, readmission rate, compliance to the protocol and morbidity. Primary endpoint was the description of the results and the identification of critical issues of large scale implementation of an ERAS program in colorectal surgery emerged in the experience of a single center. Secondary endpoint was the identification of interventions that have been proven to be effective for facilitating the transition from traditional care pathways to a multimodal management protocol according to ERAS principles in colorectal surgery at a single center. RESULTS: During the initial pilot study (March 2009 to December 2010; 47 patients) conducted by a dedicated multidisciplinary team, compliance to the items of ERAS protocol was 93%, with a median length of hospital stay (LOS) of 3 d. Early anastomotic fistulas were observed in 2 cases (4.2%), which required reoperation (Clavien-Dindo grade IIIb). None of the patients had been discharged before the onset of the complication, which could therefore receive prompt treatment. There were also four (8.5%) minor complications (Clavien-Dindo grade II). Thirty days readmission rate was 4%. Perioperative mortality was nil. After implementation of the protocol throughout the Hospital in unselected patients (May 2012 to December 2012; 147 patients) compliance was 74%, with a median LOS of 6 d. Early anastomotic fistulas were observed in 11 cases (7.7%), 5 (3.5%) of which required reoperation (Clavien-Dindo grade IIIb). Two early anastomotic fistulas were treated by radiologic/endoscopic manoeuvres and 4 were treated conservatively. There were also 36 (25.2%) minor complications, 21 (14.7%) of which were Clavien-Dindo grade II and 15 (10.5%) of which were Clavien-Dindo grade I. Only two patients whose course was adversely affected by the development of an anastomotic leak had been discharged before the onset of the complication itself, requiring readmission. Readmission rate within 30 d was 4%. Perioperative mortality was 1%. CONCLUSION: Our results confirm that introduction of an ERAS protocol for colorectal surgery allows quicker postoperative recovery and shortens the length of stay compared to historical series.

Retroperitoneal sarcoma: is it time to change the surgical policy?

BACKGROUND: Complete tumor resection is the mainstay of treatment for retroperitoneal sarcoma (RPS), but the size and quality of surgical margins for radical resection in RPS are unknown. They are believed to be pushing tumors, but recently, aggressive surgical policies leading to multivisceral resection have seemed to suggest better local control compared with simple tumor resection. We analyzed a single-institution series of RPS to provide information useful to surgical decision-making. METHODS: From 1996 to 2008, 77 patients referred to our institution underwent surgery for primary RPS. Thirty tumors were classified as liposarcoma, and 20 as leiomyosarcoma. Potential prognostic factors were tested retrospectively. Number and pathologic status of resected organs were assessed. RESULTS: 151 organs were resected. Ninety-two were involved by the tumor (60.9%). Liposarcoma involved 48 of 77 organs resected for this histotype (62.3%). Infiltrative pattern was observed in 39/92 organs, and expansive pattern in 53/92 viscera. The infiltrative pattern was more often observed in leiomyosarcoma and non-lipogenic tumors. The expansive pattern was more often observed in liposarcoma. Psoas was the organ most often involved by infiltrative pattern (12/14); the kidney was the organ most often involved by expansive pattern (19/28). 80% of patients had at least one viscera infiltrated by the tumor. CONCLUSIONS: This series, in which an aggressive surgical policy was adopted along with extensive pathologic sampling, shows that RPS has a high rate of viscera infiltration. This growth pattern is characteristic of well-differentiated liposarcoma too. These pathologic data should be considered when planning surgical strategy.

Neutropenic enterocolitis: is there a right timing for surgery? Assessment of a clinical case.

Neutropenic enterocolitis is a severe and potentially life-threatening complication that may affect patients undergoing chemotherapy for acute leukemia or lymphoma. These patients may develop systemic sepsis through bacterial or fungal translocation across the intestinal wall. In many cases neutropenic enterocolitis is confined to the cecum, but the entire colon is sometimes involved. Most patients are treated conservatively because an improvement occurs when the absolute neutrophil count rises. However, a surgical approach consisting of resection of the colon may sometimes be necessary, even in patients with complete aplasia and a high risk of complications. The right time to perform surgery is hard to define. Intestinal wall thickness, evaluated by ultrasound, is an important prognostic factor which could act as a guide to surgical indication. We analyze a case of neutropenic enterocolitis which occurred in a patient with acute myeloid leukemia during chemotherapy and we suggest that, as well as intestinal wall thickness, hemodynamic worsening should be considered an indication for surgery.

[Integrated treatments of rectal carcinoma (review)]. / I trattamenti integrati del carcinoma rettale (review).

We have reviewed the international literature regarding the treatment of rectal carcinoma. Over the last decades the evolution of treatment methods has led to a drastic fall in the incidence of local recurrences which has gone from a wide range (15-40%) to a much lower figure (10%). This favourable result has been reached also due to improvement in surgical techniques (total mesorectal excision) and to the use of an association of preoperative radio and chemotherapy. However, the drugs and dosage of these as well as of the RT still have to be defined. In our experience the integrated treatment has brought a downstaging of the T in 60% of cases and of the N in 15%.