Angelo Di Giorgio

Cytoreductive surgery (peritonectomy procedures) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of diffuse peritoneal carcinomatosis from ovarian cancer

Because of scarce data from larger series and nonhomogeneous selection criteria, further information is needed on peritonectomy with hyperthermic intraperitoneal chemotherapy (HIPEC) in managing patients with ovarian peritoneal carcinomatosis.

Prevention of Peritoneal Metastases from Colon Cancer in High-Risk Patients: Preliminary Results of Surgery plus Prophylactic HIPEC

The study compared the outcome in patients with advanced colonic cancer at high risk of peritoneal metastases (mucinous or signet-ring cell) without peritoneal or systemic spread, treated with standard colectomy or a more aggressive combined surgical approach. The study included patients with colonic cancer with clinical T3/T4, any N, M0, and mucinous or signet ring cell histology. The 25 patients in the experimental group underwent hemicolectomy, omentectomy, bilateral adnexectomy, hepatic round ligament resection, and appendectomy, followed by HIPEC. The control group comprised 50 patients treated with standard surgical resection during the same period in the same hospital by different surgical teams. Outcome data, morbidity, peritoneal recurrence rate, and overall, and disease-free survival, were compared. Peritoneal recurrence developed in 4% of patients in the experimental group and 22% of controls without increasing morbidity (P < 0.05). Actuarial overall survival curves disclosed no significant differences, whereas actuarial disease-free survival curves showed a significant difference between groups (36.8 versus 21.9 months, P < 0.01). A more aggressive preventive surgical approach combined with HIPEC reduces the incidence of peritoneal recurrence in patients with advanced mucinous colonic cancer and also significantly increases disease-free survival compared with a homogeneous control group treated with a standard surgical approach without increasing morbidity.

Lung cancer and skeletal muscle metastases

Skeletal muscle metastases from lung cancer are rare, and the optimal treatment strategy is unknown. Three cases of skeletal muscle metastases from lung cancer are described. In 2 patients surgical biopsy of muscle swelling disclosed the presence of the lung tumor; the first patient underwent lung resection to remove the primary lesion, the second was not operable because of the metastatic extension of the disease. In the third patient muscle metastasis was observed and excised after lung resection. Adenocarcinoma, squamous cell, and small cell carcinoma were the histologic types diagnosed. Various regimens of radiotherapy and chemotherapy were adopted. Survival times were 3, 6, and 30 months.

Ultrasound guided excisional biopsy of non‐palpable breast lesions: technique and preliminary results

OBJECTIVE To develop a simple and accurate technique of incisional biopsy under ultrasonographic guidance to aid the histological diagnosis of non-palpable lesions of the breast DESIGN Open prospective study. SETTING Teaching hospital, Italy. SUBJECTS 35 patients who presented to this hospital with 42 non-palpable lesions diagnosed by echography or mammography during 18 month period 1995-1996. INTERVENTIONS Creation of a pocket in the breast in which the transducer of the ultrasound scanner was inserted to guide the surgeon while an excision biopsy was taken. MAIN OUTCOME MEASURES Histological diagnosis, and quality of scar. RESULTS Mean (SD) diameter of the lesions was 11.6 (3.15) mm on the ultrasound scan, that of the biopsy specimens was 18.1 (5.82) mm, and that of the histological specimens 9.7 (3.52) mm. 29 lesions showed fibrocystic mastopathy with apocrine metaplasia, 10 fibroadenomas, 2 invasive ductal carcinoma, and 1 atypical duct hyperplasia. There were no unsightly scars. CONCLUSIONS We have developed a simple and accurate technique for incisional biopsy under ultrasound control.

Metastasis of Pleural Mesothelioma Presenting as Bleeding Colonic Polyp

We report the case of a 72-year-old woman with metastatic malignant mesothelioma presenting as right colonic polyp. She was diagnosed with malignant pleural mesothelioma 2 years previously and underwent surgery, radiotherapy, and chemotherapy. After 2 years with a negative follow-up, she was admitted to the infectious disease department for malaria and severe anaemia. A computed tomographic scan and a colonoscopy showed a huge bleeding polypoid lesion in the right colon diagnosed as adenocarcinoma. She underwent a right hemicolectomy; a pathologic examination found neoplastic cell population positive to anti-cytokeratin7, anti-calretinin, anti-vimentin, and negative for anti-cytokeratin 20, MOC-31, and thyroid transcription factor 1, providing a diagnosis of metastatic mesothelioma.

Septic bilateral pulmonary candidiasis successfully treated with anidulafungin therapy in two patients with peritoneal carcinomatosis

Sir, Although recovery of Candida from the respiratory tract is common, primary Candida pneumonia is an extremely rare occurrence, and has been described only in patients with severe forms of immunosuppression. Here we describe two patients with peritoneal carcinomatosis undergoing neoadjuvant chemotherapy plus extensive surgery who developed bilateral pulmonary candidiasis. Written consent for publication was obtained from each patient. Case 1: a 67-year-old woman was admitted to our institution with a diagnosis of peritoneal carcinomatosis from lower rectal cancer. She underwent neoadjuvant systemic chemotherapy (FOLFOX; leucovorin, fluorouracil and oxaliplatin) and extensive surgery, including lower rectal resection with colo-anal anastomosis, pelvic and parietal peritonectomy, omentectomy, bilateral hysteroadnexectomy and intra-peritoneal hyperthermic chemotherapy (IPHC) with oxaliplatin. She had a port-a-cath (PAC) for chemotherapy in place and a central venous catheter (CVC) placed in the internal jugular vein. On day 9 the patient developed fever (398C) and signs of inflammatory systemic response. After three sets of blood cultures were drawn, empirical therapy with meropenem, vancomycin and fluconazole was started. On day 10 the blood cultures were negative and the CVC tip culture grew only two to three colonies of Candida spp. The patient developed severe respiratory failure, and chest CT demonstrated multiple, peripheral, nodular lesions involving both lungs (see Figure 1). Bronchoalveolar lavage (BAL) culture yielded Candida spp. On day 12 all blood cultures and culture of the removed PAC yielded Candida albicans plus Candida famata, and anidulafungin therapy was started at a loading dose of 200 mg followed by 100 mg every 24 h. Transoesophageal echocardiography (TEE) performed at the time of blood culture positivity excluded infectious endocarditis (IE). Fundoscopic examination revealed retinal exudates, and voriconazole was added to the therapy. After 15 days of anidulafungin a new CT scan showed disappearance of lung lesions, and the patient was discharged after 26 days of hospital stay. The 8 month follow-up was negative for relapse of infection. Case 2: a 61-year-old woman was admitted to our institution with a diagnosis of peritoneal carcinomatosis from advanced gastric cancer. The patient was initially treated with neoadjuvant chemotherapy (cisplatin, fluorouracil and taxotere), and then underwent surgical intervention of peritonectomy, total gastrectomy plus IPHC with oxaliplatin. She had a PAC in place used for intravenous chemotherapy. After a post-operative intensive care unit (ICU) stay of 5 days the patient was transferred to a general ward. However, on day 12 the patient presented with low-grade fever, anorexia and leucocytosis. Multiple sets of blood cultures were drawn. On day 15 the patient developed severe sepsis and respiratory failure requiring non-invasive mechanical ventilation. Cultures of PAC, BAL and blood all grew C. albicans. A chest CT showed bilateral infiltrates. IE was ruled out by TEE. The patient was treated for 14 days with anidulafungin therapy (loading dose of 200 mg and then 100 mg every 24 h) followed

Proactive Management for Gastric, Colorectal and Appendiceal Malignancies: Preventing Peritoneal Metastases with Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

An integrated treatment strategy using peritonectomy procedures plus hyperthermic intraperitoneal chemotherapy (HIPEC) is now a clinical standard of care in selected patients with peritoneal metastases and primary peritoneal tumors. This comprehensive approach can offer many patients, who hitherto had no hope of cure, a good quality of life and survival despite limited morbidity. The increasingly successful results and chance of interfering in the natural history of disease has prompted research to develop for some clinical conditions a therapeutic strategy designed to prevent malignant peritoneal dissemination before it becomes clinically evident and treat it microscopically (tertiary prevention). The main factor governing successful cytoreductive surgery and predicting outcome is the extent of peritoneal spread assessed with the peritoneal cancer index (PCI). In peritoneal metastases from colorectal and gastric cancer the PCI score acquires a specific role acting as the cut-off between patients who can undergo curative surgery or palliation. Long-term results show that the only group enjoying favorable results are patients with limited disease (a statistical minority). By applying to appropriately selected patients with primary malignancies a proactive management strategy including HIPEC we can treat patients with microscopic peritoneal dissemination and therefore at PCI 0. Among treated conditions pseudomyxoma peritonei enjoys the best results. But a major future advance comes from identifying among lesions at major risk of pseudomyxoma.

Depth of colorectal-wall invasion and lymph-node involvement as major outcome factors influencing surgical strategy in patients with advanced and recurrent ovarian cancer with diffuse peritoneal metastases

BackgroundMore information is needed on the anatomopathological outcome variables indicating the appropriate surgical strategy for the colorectal resections often needed during cytoreduction for ovarian cancer.MethodsFrom a phase-II study cohort including 70 patients with primary advanced or recurrent ovarian cancer with diffuse peritoneal metastases treated from November 2000 to April 2009, we selected for this study the 52 consecutive patients who needed colorectal resection. Data collected included type of colorectal resection, peritoneal cancer index (PCI), histopathology (depth of bowel-wall invasion and lymph-node spread), cytoreduction rate and outcome. Correlations were tested between possible prognostic factors and Kaplan-Meier five-year overall and disease-free survival. A Cox multivariate regression model was used to identify independent variables associated with outcome.ResultsIn the 52 patients, the optimal cytoreduction rate was 86.5% (CC0/1). In all patients, implants infiltrated deeply into the bowel wall, in 75% of the cases up to the muscular and mucosal layer. Lymph-node metastases were detected in 50% of the cases; mesenteric nodes were involved in 42.3%. Most patients (52%) had an uneventful postoperative course. Operative mortality was 3.8%. The five-year survival rate was 49.9% and five-year disease-free survival was 36.7%. Cox regression analysis identified as the main prognostic factors completeness of cytoreduction and depth of bowel wall invasion.ConclusionsOur findings suggest that the major independent prognostic factors in patients with advanced ovarian cancer needing colorectal resections are completeness of cytoreduction and depth of bowel wall invasion. Surgical management and pathological assessment should be aware of and deal with dual locoregional and mesenteric lymphatic spread.

Bilateral uveitis with hypopyon as a presenting symptom of metastatic peritoneal carcinomatosis.

Purpose To report the association between bilateral uveitis with hypopyon and metastatic peritoneal carcinomatosis. Methods A 76-year-old woman presented bilateral diffuse uveitis with hypopyon. She was in good health. She reported breast cancer history 20 years before with no recurrence of tumor at periodic examinations. Results The patient had visual acuity of count fingers in both eyes, hypopyon, and vitritis with no chorioretinal lesions. After 1 week of steroids, visual acuity and intraocular inflammation improved significantly. Given the late age at uveitis onset, clinical picture of uveitis, and breast cancer history, we suspected associated malignancy. Total body computed tomography revealed peritoneal carcinomatosis, which was removed 1 month later. After 12 months, visual acuity was 0.8 bilaterally and bilateral uveitis resolved completely. Conclusions Excluding a masquerade syndrome and a paraneoplastic syndrome on the basis of clinical features, uveitis represents an immune response to the concurrent tumor. The good response to steroid therapy is in accordance with this hypothesis. This is the first case of uveitis with hypopyon as presenting symptom of a metastatic peritoneal carcinomatosis developing 20 years after the removal of primitive breast cancer.

Neoadjuvant chemotherapy fails to improve survival in advanced ovarian cancer: but is it the real culprit?

To the Editor: T study by Milam et al 1 and other recently published articles on advanced epithelial ovarian cancer all report higher rates of optimal cytoreduction in patients who receive neoadjuvant chemotherapy than in those who undergo primary surgery. Although these studies again confirm the essential prognostic role of cytoreductive surgery in advanced ovarian cancer, none of them succeed in explaining why increasing the rate of optimal cytoreduction leaves survival almost unchanged. One explanation is that regardless of neoadjuvant chemotherapy, optimal cytoreduction, leaving 1 cm or less of residual tumor, rather than complete cytoreductive surgery, is not enough to improve survival. Management of patients with advanced epithelial ovarian cancer (stages IIIC and IV), such as those treated by Millam et al, comprises 2 basic treatment strategiesVchemotherapy and surgery. Whereas neoadjuvant or adjuvant chemotherapy is a fully standardized procedure, surgery remains open to wide patient-related and surgeon-related variability. Standard debulking surgery envisages bilateral hysteroadnexectomy, appendectomy, omentectomy, iliacobturator, and peri-aortocaval lymphadenectomy, associated with less standardized procedures to resect other organs and structures frequently involved by the malignant spread. Given the wide variability in the severity and location of malignant spread within the abdominal cavity, the type of resection needed for debulking surgery therefore varies equally widely. The extent and quality of multiorgan resections depend closely on the individual surgeon’s skill and cytoreductive aim. One of the recently published multicenter studies enrolling a large study sample clearly depicts the wide variability in surgical approaches used for debulking and cytoreduction many often failing to meet the standard requirements for treating ovarian cancer. Insofar as all investigators agree that the most reliable prognostic factor in advanced epithelial ovarian cancer is the degree of cytoreduction, the most pressing problems to face are identifying the best surgical strategies for multiorgan resection, finding reliable criteria for assessing endoperitoneal malignant spread, and, most importantly, improving the surgical skills and procedures needed to achieve complete cytoreduction. We should focus our interest on peritonectomy procedures to obtain complete cytoreduction combined with intraperitoneal hyperthermic chemotherapy to treat microscopic residual disease. Current evidence suggests that this complex strategy does much to benefit outcome. Angelo Di Giorgio, MD Paolo Sammartino, MD, PhD Daniele Biacchi, MD, PhD Department of Surgery ‘‘Pietro Valdoni’’ Sapienza University of Rome Rome, Italy angelo.digiorgio@uniroma1.it