Clinical Course and Risk Factors for In-Hospital Mortality of 205 Patients with SARS-CoV-2 Pneumonia in Como, Lombardy Region, Italy.

The aim of this study is to explore risk factors for in-hospital mortality and describe the effectiveness of different treatment strategies of 205 laboratory-confirmed cases infected with SARS-CoV-2 during the Lombardy outbreak. All patients received the best supportive care and specific interventions that included the main drugs being tested for repurposing to treat COVID-19, such as hydroxychloroquine, anticoagulation and antiviral drugs, steroids, and interleukin-6 pathway inhibitors. Clinical, laboratory, and treatment characteristics were analyzed with univariate and multivariate logistic regression methods to explore their impact on in-hospital mortality. Univariate analyses showed prognostic significance for age greater than 70 years, the presence of two or more relevant comorbidities, a P/F ratio less than 200 at presentation, elevated LDH (lactate dehydrogenase) and CRP (C-reactive protein) values, intermediate- or therapeutic-dose anticoagulation, hydroxychloroquine, early antiviral therapy with lopinavir/ritonavir, short courses of steroids, and tocilizumab therapy. Multivariable regression confirmed increasing odds of in-hospital death associated with age older than 70 years (OR 3.26) and a reduction in mortality for patients treated with anticoagulant (-0.37), antiviral lopinavir/ritonavir (-1.22), or steroid (-0.59) therapy. In contrast, hydroxychloroquine and tocilizumab have not been confirmed to have a significant effect in the treatment of SARS-CoV-2 pneumonia. Results from this real-life single-center experience are in agreement and confirm actual literature data on SARS-CoV-2 pneumonia in terms of both clinical risk factors for in-hospital mortality and the effectiveness of the different therapies proposed for the management of COVID19 disease.

Ramirez's abdominoplasty technique combined with intraperitoneal chemohyperthermia after surgical cytoreductive procedures for the treatment of advanced intraperitoneal cancer in patients with ventral hernia.

Patients affected by peritoneal carcinomatosis are frequently submitted to repeated laparotomies to reduce intra-abdominal bulky lesions and to enhance the systemic chemotherapeutic action. Aim of our study is to evaluate feasibility and results of cytoreductive surgery and intraperitoneal chemohypertermic (IPCH) perfusion combined with Ramirez's abdominoplastic technique in selected patients with voluminous ventral hernias.At the same time, we support the hypothesis that Ramirez' technique would allow a normal intra-abdominal pressure leading to an optimal capability of penetration of chemotherapeutic agents in IPCH.From January 1998 to December 2003, 30 patients were submitted to a surgical debulking and IPCH through a laparotomic approach involving a ventral hernia. After extensive cytoreductive surgery, we closed the large abdominal wall damage with Ramirez's abdominoplasty technique, followed by IPCH. The technique described by Ramirez uses bilateral muscle flap complexes transposed medially to reconstruct the central abdominal wall without using meshes to supply or reinforce the abdominal reconstruction.A total of 23 patients (76.7%) were completely cytoreducted and subjected to IPCH. Postoperative mortality was 1/30 (3.3%). Major morbidity was 5/30 (16.7%). After a mean follow-up of 3 years, no sign of recurrent ventral hernia was noted in the survivors.This study suggests that surgical debulking combined with IPCH is feasible in patients with a previously large abdominal wall defect using the functional Ramirez's abdominoplasty technique. The reconstructive technique allows a regular IPCH procedure without recurrence of the ventral hernia confirmed by clinical examination and abdominal computed tomography.

Aggressive sebaceous carcinoma of the head.

Cutaneous sebaceous carcinoma (SC) is a rare malignancy deriving from the adnexal epithelium of the sebaceous glands. Periorbital SC is approximately three times more common than extraorbital cutaneous SC. Extraocular SC is reported to be less aggressive than orbital sebaceous carcinoma and rarely metastasizes. We report a case of sebaceous carcinoma of the scalp, characterised by highly aggressive behaviour and huge invasion of the intracranial space. The patient was a 79-year-old woman who developed an infiltrating sebaceous carcinoma followed by lymph-node metastases shortly after excision of the primary lesion, resulting in death. In this case, aggressive biological behaviour was observed in a carcinoma arising in an extraorbital area, although it has traditionally been considered a less aggressive neoplasm.

Cytoreductive surgery combined with intraperitoneal chemohyperthermia for the treatment of advanced colon cancer.

BACKGROUND: Chemohyperthermic peritoneal perfusion (CHPP) after extensive cytoreductive surgery is a possible choice as a regional treatment for peritoneal carcinomatosis (PC). The multicentric France EVOCAPE 1 study demonstrated that the median overall survival of patients with colon peritoneal carcinomatosis subjected to conventional surgical and/or chemotherapeutic treatment was 5.2 months. Historically, mitomycin C is the drug of choice in the treatment of intraperitoneal carcinomatosis from colon cancer. METHODS: Twenty-five patients affected by stage IV colon cancer with only peritoneal involvement and a prior completion of at least a partial first cycle of systemic chemotherapeutic and/or surgical treatment (24 patients) were enrolled. Immediately following extensive cytoreductive surgery, early postoperative closed abdomen CHPP was performed. RESULTS: Complete surgical cytoreduction (CC0-CC1) was obtained in 22 patients. Postoperative mortality was 1 out of 25 (4%). Major postoperative morbidity was 6 out of 25 (24%). Median overall survival estimated by Kaplan-Meier curve was 30.3 months. Locoregional progression-free survival was 17.3 months. Of all the patients 64% and 40% were alive after 1 and 2 years respectively. CONCLUSIONS: In referral centers CHPP after optimal surgical debulking is a safe procedure for peritoneal carcinomatosis from colonic cancer. Locoregional control was obtained in the majority of the pretreated patients and 1-year survival was statistically improved. A closed abdomen CHPP procedure lasting 1 hour and standard mitomycin C at a dosage of 15 mg/m(2) is probably as efficacious as other hyperthermic procedures, using higher mitomycin C dosages, with a comparable or lower number of cases of side effects. These results, as in other published phase II studies, justify future randomized trials to assess definitively the role of CHPP in the treatment of locally advanced colon neoplasms in western countries.

Gemcitabine and oxaliplatin in patients with pancreatic adenocarcinoma: clinical and pharmacokinetic data.

OBJECTIVES: This phase 2 study evaluated clinical efficacy, toxicity, and pharmacokinetics of combination gemcitabine (GEM) and oxaliplatin (OXA) in patients with advanced pancreatic adenocarcinoma. METHODS: Of 30 eligible patients, 20 had metastatic disease and 10 had nonmetastatic unresectable locally advanced disease. Gemcitabine 1000 mg/m2 as a 10 mg/m2/min intravenous infusion on day 1 and oxaliplatin 100 mg/m2 as a 2-hour intravenous infusion on day 2 were administered every 2 weeks. Pharmacokinetics were evaluated in 11 patients by administering the 2 drugs in opposing sequences GEM-OXA (GEM day 1, OXA day 2) and OXA-GEM (OXA day 1, GEM day 2). RESULTS: Of 30 patients evaluated, 9 had a partial response, 11 had disease stabilization, and 10 had disease progression. Median progression-free survival and overall survival were 5.5 and 9.5 months, respectively. The 1-year survival was 37% for all patients. This study revealed no significant pharmacokinetic interaction between the 2 drugs in the GEM-OXA or in the OXA-GEM sequence. CONCLUSIONS: The combination of GEM and OXA was well tolerated and showed a promising activity in patients with advanced pancreatic adenocarcinoma; no sequence-dependent pharmacokinetic interaction occurred when comparing the GEM-OXA versus the OXA-GEM sequence, with a 24-hour interval.

Low-molecular-weight heparin and calcium heparin in thrombosis prophylaxis in patients with percutaneous arterial and venous ports for colorectal liver metastases.

STUDY OBJECTIVE: The evaluation of low-molecular-weight heparin use to prevent arterial and venous thrombosis in patients with indwelling arterial Port-a-Cath implants. METHODS: From 1996 to March 2003 we placed 370 indwelling hepatic arterial catheters with a minimally invasive approach. The left distal subclavian artery was approached from beneath the left clavicle, then an angiographic study of the tumoral vascular district was performed and the gastroduodenal artery was occluded by an embolus. A polyurethane catheter was introduced distally into the hepatic artery and connected to a reservoir through a 3-4 cm long subcutaneous tunnel. In 90 patients a venous Port-a-Cath was placed for concurrent systemic chemotherapy. All 370 patients received regional chemotherapy and were treated with calcium heparin at a dose of 5000 IU twice a day and with low-molecular-weight heparin at prophylactic doses (dalteparin 2500 IU or nadroparin 3000 IU) during catheter permanence to prevent hepatic artery thrombosis. Intra-arterial trans-port radionuclide scans using technetium-99m-labeled micro-aggregated albumin were performed monthly to check the infusion distribution and hepatic artery patency. In the presence of anomalous patterns, thrombosis, pulmonary embolism or other complications, angiography and/or other diagnostic studies were performed to determine the cause of the vascular event and the local or systemic symptoms. The mean arterial and venous Port-a-Cath permanence times were 6 and 8 months, respectively. RESULTS: We observed episodes of hepatic artery thrombosis in 4.3% of patients. Three of these 17 patients were successfully treated by intra-arterial thrombolysis using urokinase. No venous thrombosis occurred as a consequence of regional and/or systemic chemotherapy, no episodes of arterial thrombosis were registered during arterial catheter permanence, nor did any hemorrhagic complications related to anti-coagulant therapy occur. Five patients treated with low-molecular-weight heparin required treatment suspension due to a platelet count of < 40,000/dL. CONCLUSION: Our experience suggests that low-molecular-weight heparin and/or calcium heparin at prophylactic doses could be useful in the prevention of arterial and venous thrombosis in patients with indwelling arterial catheters or venous Port-a-Cath treated with regional or systemic chemotherapy for hepatic metastases from colorectal cancer. The homogeneity of the patient group and the use of analogous chemotherapeutic drugs (fluoropyrimidines) avoided statistical contamination related to differences between kinds of cancer and between the chemotherapeutic agents used.

Cytoreductive surgery and intraperitoneal chemohyperthermia for recurrent peritoneal carcinomatosis from ovarian cancer.

Aggressive surgical cytoreduction has been shown to have a positive impact on survival of patients with ovarian cancer. After first-line chemotherapy, 47% of patients relapse within 5 years, and median survival after second line chemotherapy is 10-15 months. Adding intraperitoneal chemohyperthermia (IPCH) to surgical cytoreduction could further control ceolomic spread of disease. The aim of this study was to determine morbidity and mortality, regional relapse-free survival and, preliminarily, overall survival after combining cytoreductive surgery with IPCH for the treatment of peritoneal carcinomatosis from ovarian epithelial cancer relapsed after prior chemotherapy. Thirty women affected with such a relapse were included. Patients underwent extensive cytoreductive surgery including tumor resections and peritonectomy, followed by intraoperative IPCH with cisplatin. Complete surgical cytoreduction down to nodules less than 2.5 mm (CC0-CC1) was obtained in 23 patients (77%). One patient died postoperatively from a pulmonary embolism. Major postoperative morbidity was 5/30 (16.7%). We registered one case of anastomotic leakage, a spontaneous ileum perforation, a postoperative cholecystitis, a hydrothorax, and one patient with bone marrow toxicity. Kaplan-Meier estimates of median locoregional relapse-free survival and median overall survival were 17.1 months and 28.1 months, respectively. Patients with CC0-CC1 had locoregional relapse-free and overall survival rates of 24.4 and 37.8 months, whereas the remainder had survival rates of 4.1 and 11.0 months. We concluded that cytoreductive surgery combined with IPCH is feasible with acceptable morbidity and mortality and seems to promise good results in selected patients affected with peritoneal carcinomatosis from ovarian cancer.

Role of different techniques for the placement of Denver peritoneovenous shunt (PVS) in malignant ascites.

The aim of the study is to evaluate 3 different techniques of Denver peritoneovenous shunt (PVS) placement. Fifty-three patients with malignant ascites underwent placement of 55 Denver PVS by a surgical (33 cases) or percutaneous (18) or laparoscopically assisted (4) procedure. There were 2 cases of postoperative mortality due to cardiac failure, and 7 cases of shunt obstruction (2 of them required replacement). Twenty patients underwent subsequent palliative treatment with chemotherapy or surgery. Complication and control of ascites rates are similar for the 3 techniques. Placement of Denver PVS for the treatment of malignant ascites appears to be a safe and useful procedure. Surgical dissection of the jugular vein is not mandatory. The percutaneous technique is the easiest, fastest, and least invasive procedure. Laparoscopic-assisted positioning is recommended if a peritoneal biopsy and/or abdominal exploration is required for a definitive diagnosis.

Intraoperative hyperthermic tissue ablation in pulmonary metastases: a case report.

AIMS AND BACKGROUND: The surgical removal of lung metastases is controversial: some authors have reported good results in terms of prognosis and disease-free interval in patients affected by multiple metastases. Recently, percutaneous hyperthermic tissue ablation (HTA) has been used under CT guidance in solitary peripheral pulmonary tumors attached or close to the parietal pleura. METHODS AND STUDY DESIGN: We report the first intraoperative HTA of a lung metastasis from colorectal carcinoma, which might pave the way for possible future application of the procedure in patients with multiple pulmonary metastases. A 64-year-old patient affected by a rectal cancer was treated by abdominal perineal amputation followed by two lines of chemotherapy. After two years two lesions appeared in the lower left pulmonary lobe and another in the lower right lobe. The patient was monitored by three-monthly thoracic and abdominal CT. The lesions were stable for one year, but in the last two months one of the suspected metastases in the left lung increased from 1 to 2 cm. This was an indication for surgical removal. A mini posterolateral thoracotomy was performed. Thanks to complete collapse of the lung with manual squeezing of the parenchyma, ultrasonography provided satisfactory visualization of the two lesions. A frozen biopsy of the larger lesion was obtained which confirmed its metastatic nature. Ultrasound-guided HTA of the larger metastasis (2 cm) was performed. Final US demonstrated the change in the metastatic pattern. The two lesions were eventually removed by wedge resection using a TA 90 stapler. Histological examination of the two lesions confirmed the coagulative necrosis of the treated metastasis. No morbidity or pulmonary problems were recorded.

Asbestos-induced peritoneal mesothelioma in a construction worker.

Occupational and environmental asbestos exposure continues to represent a public health problem, despite increasingly restrictive laws adopted by most industrialized countries. Peritoneal mesothelioma is a rare and aggressive asbestos-related malignancy. We present the case of a 65-year-old man who developed recurrent ascites after having been exposed to asbestos in the building industry for > 40 years. Liver function and histology were normal. Abdominal computed tomography initially excluded the presence of expansive processes, and no abnormal cells were found in the ascitic fluid. Laparoscopy showed diffuse neoplastic infiltration of the peritoneum. Histopathology of bioptic samples revealed epithelioid neoplastic proliferation with a tubulopapillary pattern, falsely suggesting metastatic adenocarcinomatosis. In consideration of the occupational history, and after further diagnostic procedures had failed to identify the hypothetical primitive tumor, immunostaining of the neoplastic tissue was performed. Results were negative for carcinoembrionary antigen and the epithelial glycoprotein Ber-EP4, whereas results were positive for the mesothelial markers cytokeratins, calretinin, epithelial membrane antigen, and HBME-1, thus leading to the correct diagnosis of peritoneal epithelial mesothelioma. The Italian Workers' Compensation Authority recognized the occupational origin of the disease. Cytoreductive surgery associated with continuous hyperthermic peritoneal perfusion (cisplatin at 42 degrees C, for 1 hr) was performed. The disease relapsed after 4 months and was later complicated by a bowel obstruction requiring palliative ileostomy. The patient died 23 months after diagnosis. This case illustrates the insidious diagnostic problems posed by peritoneal mesothelioma, a tumor which often simulates other malignancies (e.g., metastatic carcinomas) at routine histopathological examination. Occupational history and immunohistochemistry are helpful for the correct diagnosis, which, in turn, is important in relation to prognosis and treatment (adoption of new integrated procedures that seem to promise prolonged survival and increased quality of life), and in relation to medicolegal issues and occupation-related compensation claims following asbestos exposure.

[Peritoneal carcinomatosis: new strategies for more efficacious treatment]. / Le carcinosi peritoneali: nuove acquisizioni per un trattamento più efficace.

The peritoneal carcinomatosis is considered an unlikely treatable disease using standard procedures as surgery or systemic chemotherapy. New improvements in the knowledge of the peritoneum are inducing to consider the mesothelium of the abdominal cavity as an organ similar to the other body organs. This new consideration, unified with the understanding of conditions permitting the implant of the tumor cell into the peritoneal space previous or during the surgical manipulation of the abdominal cancers, leads to the application of news strategies as the advanced cytoreduction with every nodes reduced less than 2.5 mm followed by the chemohyperthermic peritoneal perfusion (CHPP). Last papers indicate improvements in overall survival and quality of the life in ovarian, colonic and gastric cancer treated with an extensive surgical debulking plus CHPP. These results induce surgeons and oncologists to avoid incorrect strategies in the treatment of peritoneal carcinomatosis originating from ovarian and gastrointestinal tumors. In case of malignant untreatable ascites a peritoneo-venous shunt allows a control of the ascites avoiding several hospital admissions for continuous fastidious and sometime dangerous paracentesis. A palliative surgical operation in selected patients effected by trained surgical group permits an improvement of the patient's conditions in more than 80% with a positive feed back on his or her psychological behavior.

Palliative treatment of malignant refractory ascites by positioning of Denver peritoneovenous shunt.

Malignant ascites is relatively common in patients with certain types of end-stage cancer. Traditional treatments based on fluid and salt restriction and diuretic therapy often are not able to contain neoplastic ascites. These patients consequently undergo repeated abdominal paracentesis, with further plasma protein loss and risk of injury to abdominal viscera. The aim of this study was to evaluate our experience with Denver peritoneovenous shunt and the outcome of patients with malignant ascites and suggest some modifications to improve device patency. From February 1997 to December 1999, 44 Denver peritoneovenous shunts were placed in 42 patients, 17 women and 25 men, aged between 38 and 77 years (mean, 62.3), affected with malignant ascites due to advanced abdominal cancer. At the time of admission, 72% of patients had pain, 88% dysphagia, 66% nausea and/or vomiting, and 83% dyspnea. Eleven patients underwent local anesthesia with lidocaine and 33 general anesthesia with rapidly metabolized drugs. In 27 cases we used the peritoneal-internal jugular right vein surgical approach and in 3 cases the peritoneal-femoral vein surgical access, joining the saphena vein to the cross. In 10 cases, a radiological positioning of the Denver peritoneovenous shunt was effected by a trans-subclavian access. Relief of ascites symptoms was obtained in 87.5% of cases, with reduction of dyspnea, an increased appetite and improved ambulation. Denver peritoneovenous shunt is a good device to relieve malignant ascites, thereby reducing the risk of complications and the number of hospital admissions due to repeated paracentesis and consequently improving the quality of life. A careful patient selection, an accurate follow-up and some device modifications could improve the shunt performance, allowing a wider application of the Denver peritoneovenous shunt.