Tommaso Cornali

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.

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.

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.

ASO Author Reflections: Peritoneal Metastases from Endometrial Cancer

Although withdrawn as a criterion for staging endometrial cancer (EC), the American Joint Committee on Cancer (AJCC) recommends the detection of neoplastic cells in peritoneal washings as level I evidence. Intraluminal tumor cells (ILTCs) in the fallopian tubes (a histological marker of transtubal spread), detected in 10–20% of ECs, were associated with aggressive tumors, positive peritoneal cytology, and decreased survival in serous EC and earlystage, low-risk EC. Some evidence suggests the need for early bilateral tubal ligation before surgical maneuvers, whereas conflicting data relates to the possible use of a uterine manipulator and removing the uterus through the vagina, all procedures theoretically correlated with possible tumor cell spillage into the peritoneum. Data from an observational retrospective cohort analysis from the National Cancer Database including women with a known cytology status and AJCC stage IA–II EC showed that positive peritoneal washing cytology indicated decreased overall survival and the need for adjuvant chemotherapy to improve outcome. PRESENT

Computerized System for Staging Peritoneal Surface Malignancies

Background Peritoneal surface malignancies (PSMs) are usually staged using Sugarbaker’s Peritoneal Cancer Index (PCI) and completeness of cytoreduction score (CC-s). Although these staging tools are essential for selecting patients and evaluating outcome after cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), both scoring models lack some anatomic information, thus making staging laborious and unreliable. Maintaining Sugarbaker’s original concepts, we therefore developed a computerized digital tool, including a new anatomic scheme for calculating PCI and CC-s corresponding closely to patients’ real anatomy. Our new anatomic model belongs in a web-based application known as the PSM Staging System, which contains essential clinical and pathological data for the various PSMs currently treated.MethodsThe new digital tool for staging PSM runs on a personal computer or tablet and comprises male and female colored anatomic models for the 13 endoabdominal regions, with borders defined according to real anatomic landmarks. A drag-and-drop tool allows users to compute the PCI and CC-s, making it easier to localize and quantify disease at diagnosis and throughout treatment, and residual disease after CRS.ConclusionsOnce tested online by registered users, our computerized application should provide a modern, shareable, comprehensive, user-friendly PSM staging system. Its anatomic features, along with the drag-and-drop tool, promise to make it easier to compare preoperative and postoperative PCIs, thus improving the criteria for selecting patients to undergo CRS plus HIPEC. By specifying the size, site, and number of residual lesions after CRS plus HIPEC, our digital tool should help stratify patients into outcome classes.

Patient Selection for Treatment

Appropriate patient selection is of primary importance to successful cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). Given the high morbidity rate associated with these combined procedures, we need to select patients who will derive maximum benefits from treatment and who carry lower risks of postoperative complications and mortality. The high morbidity and mortality rates, especially in treatment groups approaching this type of surgery for the first time, have raised concern and often criticism [1, 2]. At the same time, besides problems linked to postoperative complications, criteria for selecting patients to undergo integrated treatment must take into account preoperative factors predicting a favorable oncologic outcome. Hence, we need to know which tumors causing peritoneal spread this combined treatments should target and to define the extent of peritoneal spread to use as a cutoff beyond which these procedures are contraindicated. To rationalize this topic, even though schematizing has its limitations, we divided selection criteria according to whether they most directly address patients’ characteristics, the site and histology underlying peritoneal spread, and the extent of peritoneal and extraperitoneal malignant spread.

Other Primary Peritoneal Surface Malignancies

Primary peritoneal surface malignancies (other than mesothelioma) are serous papillary carcinoma (PPSPC) and desmoplastic small round cell tumor (DSRCT). According new histogenetic theories, PPSPC and ovarian cancer (OC) originate from the tubal epithelium. Primary treatment in foreseen as being the application of maximal cytoreduction (peritonectomy procedures) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Evaluation of results must be done using the staging system comprising Peritoneal Cancer Index (PCI) and Completeness of Cytoreduction (CC) score. DSRCT is a rare and aggressive neoplasm, and patients typically present with an advanced stage with multiple peritoneal-based lesions. Despite multiple therapeutic strategies that include chemotherapy, aggressive debulking surgery, and abdominal-wall radiation, durable remission remains rare. A new staging system is proposed by the MD Anderson Cancer Center in the US, where peritonectomy procedures plus HIPEC are being applied with interesting results.

Rationale for Integrated Procedures: Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Combined

Diffuse peritoneal malignancy raises major therapeutic problems and puts the patient’s life at high risk. In the past, systemic chemotherapy regimens functioned as a purely palliative approach, and palliative surgery aimed merely at reducing the symptoms, being unable to alter the natural course of the disease [1]. At the beginning of the 1990s, thanks to Sugarbaker’s pioneering efforts, research began to develop integrated procedures for treating peritoneal surface malignancies based on a therapeutic approach. This approach involved cytoreductive surgery (CRS) (peritonectomy procedures) combined with perioperative intraperitoneally administered chemotherapy (IP-CHT)—eventually integrated with hyperthermia—done immediately after surgical cytoreduction ended [hyperthermic intraperitoneal chemotherapy (HIPEC)], or during the early postoperative course [early postoperative intraperitoneal chemotherapy (EPIC)] [2]. The therapeutic rationale underlying integrated treatment originates from advances in systemic chemotherapy and improved knowledge about the pharmacological mechanisms underlying endoperitoneal drug delivery. The rationale for cancer chemotherapy hinges upon several well-known theoretical hypotheses. According to the Gompertzian cellular kinetic model (the tumor-growth profile can be depicted as an S-shaped curve), a tumor initially grows slowly and then rapidly becomes fast growing [3]. As the tumor enlarges, its blood supply and growth slows down, and a larger tumor cell percentage gradually enters a nonproliferative cell-cycle stage (Fig. 8.1).

Surgery in Multimodal Treatment of Cancer: Peritoneal Carcinomatosis

Until recent years a diagnosis of peritoneal carcinomatosis (PC) from intra-abdominal solid tumors carried a uniformly fatal prognosis, often within weeks or months. Since the 1980s, following the intuition of an American surgeon, Paul Sugarbaker, combined treatment modalities of PC have developed considerably. Since the first pioneering approaches on the treatment of “pseudomyxoma peritonei”