Short-term outcome of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy used as treatment of colo-rectal carcinomatosis: a multicentric study.

The aim of this study is to assess the morbidity and mortality related to cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colo-rectal carcinomatosis. A retrospective multi-institutional study from seven Italian Centers was performed. One hundred and seventy-two patients, submitted to cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) to treat carcinomatosis of colorectal origin, were recorded. Postoperative morbidity was evaluated in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Post-operative mortality was evaluated as patients' death within 60 days from surgical procedures. Predictors of morbidity were evaluated with univariate and multivariate analyses. Post-operative morbidity occurred in 83 patients (48.3%): grades 1-2 in 29 cases (16.9%), and grades 3-4 in 54 (31.4%). Mortality occurred in four cases (2.3%). Number of anastomoses (OR 1.45; 95% CI 1.05-2.00; p = 0.024), number of blood transfusions (OR 1.31; 95% CI 1.11-1.54; p = 0.001) and chemotherapy regimen [Oxaliplatin (OX): OR 2.87; 95% CI 1.22-6.75; p = 0.015] remained, in multivariate analysis, in a statistically significant correlation with overall morbidity. The only variable that was proven to have statistically significant correlation with 3-4 morbidity was the number of blood transfusions (OR 1.25; 95% CI 1.07-1.46; p = 0.005). Morbidity and mortality do not preclude the use of CRS plus HIPEC in the treatment of peritoneal carcinomatosis of colorectal origin.

Short-term outcome of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: preliminary analysis of a multicentre study.

AIM: To assess the incidence of morbidity and mortality of Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy. PATIENTS AND METHODS: A retrospective multicentric study was performed. Six hundred and eighty-three patients were recorded. Predictors of morbidity and mortality were evaluated with univariate and multivariate analysis. RESULTS: In univariate analysis, older age, Eastern Cooperative Oncology Group score, a greater value of Peritoneal Cancer Index (PCI) and sub-optimal cytoreduction were correlated with higher mortality, while older age, presence of ascites, ovarian origin of carcinomatosis, closed technique, a greater value of PCI, longer operative time and sub-optimal cytoreduction were predictors of higher morbidity. In multivariate analysis, older age and a greater value of PCI were correlated with higher mortality; older age, ovarian origin of tumor, presence of ascites, closed technique and longer operative time were predictors of higher morbidity. CONCLUSION: Careful patient selection has to be performed to improve clinical outcomes.

Treatment of peritoneal carcinomatosis from colonic cancer by cytoreduction, peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC). Experience of ten years.

INTRODUCTION: Peritoneal carcinomatosis (PC) is one of the routes of dissemination of abdominal neoplasms and is generally considered a lethal disease, with a poor prognosis by conventional chemotherapeutic treatments. While systemic chemotherapy has little impact on the treatment of peritoneal disease, some centers have reported encouraging results with cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). This approach is based on surgical cytoreduction of the primary tumour, peritonectomy (stripping of implants on the peritoneal surface) and HIPEC. The rationale of this treatment, after macroscopic disease removal, is to obtain an elevated and persistent drug concentration in the peritoneal cavity, with limited systemic effects. Many studies have reported encouraging results on overall survival (OS) and the disease-free interval in patients affected by PC. PATIENTS AND METHODS: From October 1997 to November 2008, 411 operations for PC were performed in our institution; in 232 cases, cytoreduction plus HIPEC was carried out. Out of 72 operations for colonic cancer: 40 cytoreductions plus HIPEC, 12 cytoreductions+ EPIC (early postoperative intraperitoneal chemotherapy) and 16 debulking or explorative laparoscopies/laparotomies were performed. For the present study, the 40 patients who had undergone cytoreduction plus HIPEC for PC of colorectal cancer (CRC) were considered. RESULTS: The complication rate was 55% (22/40) and mortality rate 2.5% (1/40). The specific features of both groups were considered for the survival curves and complication rates, with special reference to the peritoneal carcinomatosis index (PCI; range 0, absence of disease to 39) and completeness of cytoreduction score (CCR; 0, no residual tumor, to CCR 3, residual nodules greater than 25 mm). In Group A, patients operated on prior to 2002, the median survival time was 16.7 months compared to 24.6 months for Group B, those operated on after 2002. The poor survival of Group A seemed to be related to higher PCI and CCR scores. CONCLUSION: Correct patient selection based on a maximum PCI of 16, associated with complete cytoreduction (CCR-0), produced encouraging results in our experience. To improve this encouraging survival outcome, it is very important to unify the surgical experience of expertise centres. Our results also suggest the need for an integrated approach to this condition to identify the correct aspect of the surgical domain and results that may be influencing the prognosis and the evolution of this patients.

Management of pseudomyxoma peritonei by cytoreduction+HIPEC (hyperthermic intraperitoneal chemotherapy): results analysis of a twelve-year experience.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare peritoneal carcinomatosis, characterized by a slowly progressive disease process with a large amount of mucus containing occasional epithelial cells. PMP is histologically classified into disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA) and an intermediate or discordant feature group (ID). Recent studies have shown that most cases of PMP originate from ruptured appendiceal tumors with progressive dissemination in the peritoneal cavity of mucin-producing epithelial cells. Encouraging results in the treatment of PMP have been reported by surgical cytoreduction of the primitive cancer, peritonectomy (stripping of implants on the peritoneal surface) and intraperitoneal hyperthermic chemoperfusion (HIPEC). In recent trials, this combined approach has been proposed as the standard treatment for PMP. PATIENTS AND METHODS: In this study, the results of twelve years single-institution experience on 60 consecutive patients affected by PMP, treated by cytoreductive surgery and the original semi-closed HIPEC technique are reported with special reference to overall survival (OS) and progression-free survival (PFS). RESULTS: The postoperative morbidity rate was 45% (27 patients); surgical morbidity was observed in 19 patients and medical complications in 9 cases. No postoperative deaths were observed. The survival data, 53 patients were analized (the last 7 were considered only for the complications rate, postoperative mortality and cancer features, not for OS or PFS because they were too recent for evaluation). At the final follow-up of the 53 patients, five and ten years OS were respectively 94% and 84.6% . DFS was 80% and 70% at five and ten years respectively. The follow-up data indicated that the survival probability may be good in patients with hystological type appendicular adenoma optimally cytoreduced (CCR-0). Interestingly if preoperative chemotherapy was performed represented a negative prognostic factor with statistically significant impact both on OS and DFS. CONCLUSION: As in other similar studies, cytoreductive surgery plus HIPEC, even when combined with an aggressive surgical procedure, is associated with an acceptable risk of postoperative complications and mortality. This combined treatment results in DFS and OS rates that are not described in the literature for surgery associated with systemic chemotherapy and, in our opinion, may be considered the gold standard treatment for this rare tumor.

Cytoreduction and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis from pseudomyxoma peritonei.

AIM: To investigate the most important aspects of hyperthermic intraperitoneal chemotherapy (HIPEC) that has been accepted as the standard treatment for pseudomyxoma peritonei (PMP), with special regard to morbidity, overall survival (OS) and disease free survival (DFS) over 10 years. METHODS: Fifty-three patients affected by PMP underwent cytoreduction (CCR) and HIPEC with a "semi-closed" abdomen technique in our institution. The peritonectomy procedure and completeness of CCR were classified according to Sugarbaker criteria. Preoperative evaluation always included thoracic and abdominal CT scan to stage peritoneal disease and exclude distant metastases. Fifty-one patients in our series were treated with a protocol based on administration of cisplatinum 100 mg/m(2) plus mitomycin C 16 mg/m(2), at a temperature of 41.5 degrees centigrade for 60 min. Anastomoses were always performed at the end of HIPEC. The mean duration of surgery was 12 h including HIPEC. Continuous monitoring of hepatic and renal functions and hydroelectrolytic balance was performed in the postoperative period. RESULTS: Twenty-four patients presented with postoperative complications: surgical morbidity was observed in 16 patients and 6 patients were re-operated. All complications were successfully treated and no postoperative deaths were observed. Risk factors for postoperative morbidity were considered to be gender, age, body surface, duration of surgery, Peritoneal Cancer Index (PCI) and tumor residual value (CC score). No statistically significant correlation was found during the multivariate analysis: only the CC score was statistically significant. The OS in our experience was 81.8%, with a DFS of 80% at 5 years and of 70% at 10 years. CONCLUSION: In our experience, even if HIPEC combined with cytoreductive surgery involves a high risk of morbidity, postoperative complications can be resolved favorably in most cases with correct patient selection and adequate postoperative care, thus minimizing mortality. The association of CCR and HIPEC can be considered as the standard treatment for PMP. The OS and DFS results confirm the validity of this combined approach for the treatment of this rare neoplasm. The impact of preoperative chemotherapy on OS, in our opinion, is due to a major aggressiveness of tumors in treated patients.

Primary osteosarcoma of the kidney with retroperitoneal hemorrhage. Case report and review of the literature.

Primary osteosarcoma of the kidney is a very rare neoplasm with a very poor prognosis and unclear histogenesis. Only 20 cases have been reported in the literature. It has a strong tendency to recur locally and spread to distant sites. We present the clinical case of a 79-year-old man affected by a primary osteosarcoma of the kidney presenting with substantial retroperitoneal tumor hemorrhage. Laparotomy revealed a massive retroperitoneal hematoma due to a bleeding large stony renal mass with multiple bizarre calcifications. The diagnosis of primary renal osteosarcoma was made on the basis of hematoxylin-eosin staining and confirmed by electron microscopy. Hematoma drainage and radical nephrectomy were performed. To our knowledge this is the first case of bleeding renal osteosarcoma reported in the literature. The most important clinical findings, the pathogenesis and the treatment modalities of this rare neoplasm are discussed.

FOLFOX-4 stop and go and capecitabine maintenance chemotherapy in the treatment of metastatic colorectal cancer.

OBJECTIVE: Patients with metastatic colorectal cancer (MCC) usually receive FOLFOX-4, or other oxaliplatin (L-HOP)-based regimens, until the occurrence of progressive disease, with an increase in the incidence of neurotoxicity which is correlated to the cumulative dose of L-HOP. The aim of this study was to evaluate if FOLFOX-4 stop and go and capecitabine maintenance chemotherapy is associated with a low incidence of severe neurotoxicity in the treatment of MCC patients. METHODS: Thirty-three patients were treated with FOLFOX-4 (L-HOP 85 mg/m(2) day 1, leucovorin 200 mg/m(2), 5-fluorouracil bolus 400 mg/m(2) and 22 h 600 mg/m(2) days 1 and 2, every 2 weeks). Patients who achieved objective response (OR) or stable disease (SD) then received oral capecitabine 2,500 mg/m(2) days 1-14 every 3 weeks; L-HOP was reintroduced as soon as progression occurred. RESULTS: Twenty-eight of the 29 patients who achieved OR or SD then received capecitabine. FOLFOX-4 was reintroduced in 18 patients (56.2%). The median response duration (RD) was 9.2 months and median progression-free survival (PFS) was 8.6 months. Twenty-eight patients (87.5%) had peripheral neuropathy during treatment, but grade 3 neurotoxicity was observed in only 1 patient (3.1%). CONCLUSIONS: FOLFOX-4 stop and go and capecitabine maintenance chemotherapy was associated with a very low incidence of grade 3 neurotoxicity. Although the number of patients enrolled was far too low for a definite conclusion, RD and PFS were comparable to those usually reported in the treatment of MCC patients.

Treatment of peritoneal carcinomatosis by cytoreductive surgery and intraperitoneal hyperthermic chemoperfusion (IHCP): postoperative outcome and risk factors for morbidity.

BACKGROUND: Cytoreductive surgery with limited or extended peritonectomy associated with intraperitoneal hyperthermic chemoperfusion (IHCP) has been proposed for treatment of peritoneal carcinomatosis (PC) from abdominal neoplasms. METHODS: Fifty-nine patients with PC from abdominal neoplasms underwent 61 treatments using this technique from January 2000 to August 2005. Surgical debulking, completed by partial or total peritonectomy, was performed in most cases. In 16 patients with positive peritoneal cytology without macroscopic peritoneal disease, IHCP was performed in order to prevent peritoneal recurrence. IHCP was carried out throughout the abdominopelvic cavity for 60 minutes using a closed abdomen technique. Intra-abdominal temperature ranged between 41 degrees C and 43 degrees C; mitomycin C (25 mg/mq) and cisplatin (100 mg/mq) were the anticancer drugs generally used, and they were administered with a flow rate of 700-800 ml/minute. RESULTS: Mean hospital stay was 13 +/- 7 (range 7-49) days. Postoperative complications occurred in 27 patients (44.3%); of these, major morbidity was observed in 17 (27.9%). The most frequent complications were wound infection (9 cases), grade 2 or greater hematological toxicity (5 cases), intestinal fistula (5 cases), and pleural effusion requiring drainage (5 cases). Reoperation was necessary in 5 patients (8.2%). One patient with multiorgan failure died in the postoperative period (mortality rate: 1.6%). Multivariate analysis of several variables identified completeness of cancer resection (CCR-2/3 vs. CCR-0/1, relative risk: 9.27) and age (relative risk: 1.06 per year) as independent predictors of postoperative morbidity. Preliminary follow-up data indicate that survival probability may be high in patients with ovarian or colorectal cancer and low in patients with gastric cancer. CONCLUSIONS: IHCP combined with cytoreductive surgery involves a high risk of morbidity, but postoperative complications could be resolved favorably in most cases with correct patient selection and adequate postoperative care. Tumor residual and advanced age significantly increase the risk of morbidity after this procedure.

Bcl-2 expression correlates with lymphovascular invasion and long-term prognosis in breast cancer.

Alterations in the mechanisms of apoptosis are responsible not only for the progression of breast cancer, but for different responses to treatment as well. Among the genes regulators of apoptosis, the tumor suppressor gene p53 and the bcl-2 gene have raised interest for their possible role as predictors of response to therapy and markers of prognosis. The purpose of our study was to prospectively analyze the prognostic value of the expression of p53 and bcl-2 genes in a series of 235 consecutive patients operated on for breast cancer at the Department of General Surgery and Surgical Oncology of the University of Siena, Italy.p53 and bcl-2 expression were evaluated by immunohistochemistry, their association with conventional clinicopathological factors was analyzed by univariate analysis and their prognostic impact was evaluated by multivariate analysis.p53 and bcl-2 were detected respectively in 15.7 and 75.7% of cases, and resulted significantly related to presence of estrogen receptors for p53 over-expression and presence of peritumor lymphovascular invasion (LVI) for bcl-2 expression. With a median follow-up of 79 months, an independent negative prognostic impact on disease free and overall survival was observed for presence of LVI, absence of bcl-2 expression and number of involved axillary lymphnodes. The expression of bcl-2 improved the prognosis of LVI positive tumors up to values similar to LVI negative cases, while its absence associated to presence of LVI resulted in a poor outcome with only 28% of patients alive at 8 years. These data may indicate that expression of bcl-2 is a marker of breast cancers with reduced capability of distant colonization, even in presence of LVI, and may be particularly useful in the clinical setting, allowing to identify a subset of patients with an high risk of relapse.

Mib-1 proliferation index is an independent predictor of lymph node metastasis in invasive breast cancer: a prospective study on 675 patients.

In order to evaluate the potential risk factors for lymph node metastasis in invasive breast cancer patients submitted to axillary dissection, 675 patients who received surgery between January 1995 and December 2002 were included in a prospective study. In all cases, MIB-1 proliferation index was investigated by immunohistochemistry. Lymph node involvement was found in 248 out of 675 patients. Univariate analysis showed that peritumoral lymphovascular invasion, pT stage, tumor multiplicity, MIB-1 proliferation index >10%, oestrogen receptor status, histological type, tumor grade and progesterone receptor status were related to a higher incidence of lymph node metastasis, with various levels of statistical significance. Multivariate analysis identified lymphovascular invasion [relative risk (RR, 7.69; p<0.001), pT stage (RR, 3.08; p<0.001), tumor multiplicity (RR, 3.89; p<0.001), and MIB-1 proliferation index (RR, 1.66; p=0.019)] as independent predictive variables. The impact of MIB-1 positivity on the incidence of lymph node metastasis was particularly evident in intermediate risk groups (pT1c, pT2 without lymphovascular invasion), as well as in grade-2 tumors. In conclusion, the MIB-1 proliferation index could provide additional information about the risk of lymph node metastasis in invasive breast cancer, and may be useful to identify grade-2 tumors with a more aggressive clinical behaviour.

[Primary ano-rectal melanoma: considerations on a clinical case and review of the literature]. / Il melanoma primitivo ano-rettale: considerazioni su un caso clinico e revisione della letteratura.

Anorectal melanoma is a rare disease (1% of all anorectal malignancies). It is characterised by aspecific symptoms and the differential diagnosis versus other lesions of the rectum and anus is often difficult. The prognosis is very poor: mean survival is about 24 months, and at diagnosis most patients present distant metastases. Surgery is suggested as being the best treatment for this disease, since radio- and chemotherapy are generally only used for palliative purposes. Long-term survival depends on the stage of the melanoma at diagnosis. The possible surgical treatments available consist in local resection, which is considered the first therapeutic choice, and abdominoperineal amputation when local resection cannot be performed, or as a palliative operation. Inguinal lymphadenectomy is indicated when the inguinal lymph nodes are involved. In this report we describe a case of anorectal melanoma in a 73-year-old woman who underwent abdominoperineal amputation as surgical palliative treatment, because of infiltration of the puborectal muscle. The case report is followed by a review of the literature.

[Cystadenoma of the pancreas: 4 cases in our clinical experience]. / Cistoadenomi del pancreas: 4 casi nella nostra esperienza clinica.

Cystic neoplasms account for about 10% of all cystic lesions of the pancreas and less than 1% of all exocrine pancreatic neoplasms. The authors report 4 cases of pancreatic cystadenoma (3 women and 1 man; mean age 59 years; range: 41-72), 2 serous and 2 mucinous, treated over the period from 1999 to 2002. The main symptoms were hypochondrial pain in two patients and diffuse abdominal pain in one while the fourth patient was asymptomatic. The patients were studied clinically by CT, echotomography and angiography. In three cases the tumours were located in the pancreatic body-tail, and in one case in the head. Serum amylase, lipase and tumour markers were all in the normal range. Only in one case was there an accurate preoperative diagnosis of tumour; in the other cases, a histological diagnosis was possible after surgical resection. Surgical treatment depended on tumour localisation: duodeno-cephalopancreatectomy for tumours in the head and distal pancreatectomy with splenectomy for tumours located in the body-tail, Lymphadenectomy at levels I and II was performed in all cases. There was no postoperative mortality and only one female patient developed postoperative acute pancreatitis. During the follow-up CT scans showed no recurrence of the pancreatic tumours. In agreement with the international literature, we hold that all cystic tumours of the pancreas should be treated by surgical therapy, above all because of the major differential diagnosis problems they continue to present. Conservative treatment is justified only for well documented asymptomatic serous cystadenomas.

[Pancreatic metastasis from clear cell renal carcinoma: a clinical case]. / Metastasi pancreatiche da carcinoma renale a cellule chiare (RCC): un caso clinico.

Renal cell carcinoma rarely metastasizes to the pancreas. In this report we describe a case of late pancreatic metastases in a seventy-year-old woman, surgically treated 21 years before for renal clear-cell carcinoma. Preoperative staging revealed the presence of four pancreatic lesions. A distal pancreatectomy and splenectomy were performed, and the postoperative period was complication-free. Histopathological analysis revealed metastases from renal clear-cell carcinoma. This case shows that in patients operated on for renal clear-cell carcinoma we have to consider the possibility of late metastases to the pancreas. Therefore, these patients should be submitted to long-term follow-up. In keeping with the current literature, we advocate aggressive surgical treatment in pancreatic metastases from renal clear-cell carcinoma.