Alessio Impagnatiello

Buschke-Löwenstein tumor with squamous cell carcinoma treated with chemo-radiation therapy and local surgical excision: report of three cases

Treatment of anorectal Buschke-Löwenstein tumor (BLT) with squamous cell carcinoma (SCC) transformation is not univocal given the rarity of the disease. BLT is characterized by its large size and tendency to infiltrate into underlying tissues. Malignant transformation can occur and it is important to identify the presence of neoplastic foci to decide the proper treatment. Our aim was to assess the effectiveness of neo-adjuvant chemo-radiation therapy (CRT) and local excision in order to avoid abdomino-perineal resection (APR). Three cases of anorectal BLT with SCC transformation are presented. All patients were HIV positive and treated with antiretroviral drugs. They underwent preoperative endoanal ultrasound, biopsies, total body tomography and anal brushing. Treatment consisted of neo-adjuvant chemo-radiation therapy (45 Gy to the pelvis plus a boost with 14.40 Gy to the primary tumor for a total of 59.40 Gy, and mitomycin-C in bolus on the first day, plus 5-fluorouracil by continuous infusion in the first and in the sixth week) and subsequent local surgical excision. During the follow-up, patients were subjected to the same preoperative diagnostic investigations and high resolution anoscopy. All patients showed a complete regression of the lesion after CRT and were treated by local surgical excision, thus avoiding permanent colostomy. In conclusion neo-adjuvant chemo-radiation therapy with local surgical excision could be considered an effective therapy in the treatment of anorectal BLT with SCC transformation to avoid APR.

High detection rate of human papillomavirus in anal brushings from women attending a proctology clinic.

OBJECTIVES To study human papillomavirus (HPV) anal infection in anal brushings from women attending a proctology clinic, and compare results with those obtained from paired cervical brushings. METHODS Women attending a university hospital proctology clinic for anal conditions or as part of a screening campaign, were enrolled consecutively, excluding those reporting previous HPV-related pathologies. HPV genotypes in anal and cervical brushings were determined by sequencing and, in most cases, type-specific viral loads were measured. RESULTS HPV DNA was detected in 28.3% of anal brushings, with 47.4% of HPV genotypes being high risk. Cervical HPV detection was at almost the same rate but HPV status was discordant in about half those women with at least one positive specimen. Abnormal cytological findings were more common in anal than in cervical samples, in particular in the proctology outpatients. Viral load measurements excluded the existence of a multiple infection with genotypes detected in discordant anal- and cervical-paired samples and showed a significant correlation between anal and cervical paired concordant samples. CONCLUSIONS The high rate of HPV detection in anal brushings that is not usually related to HPV positivity in cervical brushings could provide support for offering HPV DNA tests to women attending proctology clinics.

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.

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.

Epidemiology: Extent of the Problem

Peritoneal carcinomatosis (PC) most commonly represents local or regional evolution of an abdominal carcinoma. Sometimes it can be synchronous with the primary tumor (primary carcinomatosis) but more often is present as recurrent disease (metachronous or secondary) after first-line treatment of the originating tumor. Patients with tumors from colon, ovary, and stomach cancer are more likely to present with PC during their clinical course. Less frequently, other abdominal malignancies, such as uterus, pancreas, small bowel, biliary, or urinary tract, can involve the peritoneum. Tumors originating from the peritoneum itself are definitely rarer: mesothelioma, pseudomyxoma peritonei (PMP), primitive peritoneal carcinoma, and desmoplastic small-round-cell tumor. PC from extra-abdominal tumors, such as lung, breast, melanoma, or peritoneal sarcomatosis, is exceptional, and few epidemiological data are available on them. Statistical analysis of worldwide cancer incidence, prevalence, and mortality rate is available on GLOBOCAN 2012 [1]. In Italy, most epidemiological data are available in the reports from the Italian Association of Tumor Registries (AIRTUM) [2], which collects data regarding incidence, prevalence, and mortality rates from all local and regional tumor registries, covering at least 34% of total population. This data is considered a high-quality regional coverage by and international ranking system (GLOBOCAN 2012 rate B).