I. Benjamin Paz

Human papillomavirus (HPV) in head and neck cancer

Certain strains of human papillomavirus (HPV) have been shown to be etiologically related to the development of uterine cervical and other genital cancers, but their role in the development of malignancies at other sites is less well established. Previous studies have shown HPV DNA in tumors of the head and neck, but its prevalence has varied depending on the detection methods and the types of tumor and/or tissue examined. This study was undertaken to estimate the frequency of HPV DNA in squamous cell carcinoma (SCC) at different sites of the esophagus, head and neck and to compare the clinical behavior of HPV positive and negative tumors.

Soft Tissue Sarcoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology.

Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for STS provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumors, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis, staging, and treatment of STS of the extremities, superficial trunk, or head and neck; outlines treatment recommendations by disease stage; and reviews the evidence to support the guidelines recommendations.

A carcinoembryonic antigen-secreting adenocarcinoma arising within a retrorectal tailgut cyst: clinicopathological considerations

Retrorectal tailgut cysts (TGC) develop from postanal fetal gut remnants. They have specific radiological and histopathological features that distinguish them from dermoid cysts, enteric duplication cysts, and teratomas. We report a patient with a carcinoembryonic antigen-producing adenocarcinoma arising within a TGC who underwent resection through a combined anterior laparotomy/posterior pelvic approach. Despite complete resection and delayed but complete functional recovery, diffusely metastatic disease was encountered 6 months after resection. Diagnostic, therapeutic, histopathological, and oncological implications of this illustrative case are discussed. It seems possible to use carcinoembryonic antigen measurements for treatment planning and for assessing treatment response for this rare disease. The described outcome also suggests that TGC can develop malignant degeneration and should be resected at the time of diagnosis.

MALIGNANT PHYLLODES TUMOR OF THE BREAST: LOCAL CONTROL RATES WITH SURGERY ALONE

PURPOSE Patients with malignant phyllodes tumors of the breast (MPTB) are routinely treated with surgery alone. We performed a retrospective study to determine local control rates based on tumor size and type of surgery performed. METHODS AND MATERIALS We reviewed records of 478 patients with MPTB treated between March 1964, and August 2005. The data were extracted from the IMPAC National Oncology Database consisting of merged tumor registries from 130 hospitals. RESULTS Median follow-up was 64 months (range, 0-410 months). Actuarial 5-year local control rates were 79.4% for 169 lumpectomy patients and 91.2% for 207 mastectomy patients treated by surgery alone. Five-year local control rates for lumpectomy based on tumor size were 91% for 0-2 cm tumors, 85% for 2-5 cm tumors, and 59% for 5-10 cm tumors. For mastectomy patients, 5-year local control rates were 100% for 0-2 cm tumors, 95% for 2-5 cm tumors, 88% for 5-10 cm tumors, and 85% for 10-20 cm tumors. Multivariate analysis of overall survival found several factors to be significant including advancing age with each decade after 50 years of age, appearance of distant metastases, larger primary tumor size, and local control vs. local recurrence (Hazard Ratio [HR] 2.5, p < 0.05). CONCLUSIONS Malignant phyllodes tumors of the breast local recurrence rates are 15% or greater for patients with tumors >2 cm treated by lumpectomy alone and tumors >10 cm treated by mastectomy alone. Adjuvant radiation therapy should be evaluated for these patients. This may be especially important because our study showed that local recurrence impacted on survival rates.

Treatment of perianal infection following bone marrow transplantation

PURPOSE: Bone marrow transplantation (BMT) is often associated with profound neutropenia. Allogeneic transplant recipients also have defects in both humoral and cellular immunity and thus are subject to increased risk of serious, often life-threatening, infection even beyond the period of granulocyte recovery. The current study was undertaken to evaluate patients who required operative intervention for perianal sepsis following BMT. METHODS: The bone marrow transplant database at a single institution was used to identify all patients diagnosed with perianal infections after autologous or allogeneic BMT. Charts were reviewed in a retrospective manner. RESULTS: Over a ten-year period ending in November 1993, 963 BMT were performed at the City of Hope National Medical Center. Twenty-four patients were diagnosed with perianal infections foEowing their transplants. Fifteen patients did not have purulent collections requiring drainage and were treated with antibiotics and supportive measures alone. Nine patients (37.5 percent) required surgical intervention between 10 and 380 days following transplantation. At the time of surgical intervention, seven patients had purulent collections and two patients had acute and chronic inflammation, tissue necrosis, and fibrosis. Of the two patients with an absolute neutrophil count less than 1,000, a purulent collection was found in one of the patients. Cultures taken from perianal abscesses were almost all polymicrobial, and the most common organisms wereEscherichia coli, Bacteroides, Enterococcus,andKlebsiella.For those patients undergoing surgical intervention, mean time to complete wound closure by secondary intention was 37.6 days; five patients healed in less than 15 days, two patients healed at 93 and 114 days, and two patients had persistent, open wounds at time of death, which was unrelated to their perianal disease. Five patients were receiving systemic steroids at time of surgical intervention; this did not appear to affect time to wound healing. CONCLUSIONS: Perianal infections are a rare complication of BMT. Majority of these infections are polymicrobial, and organisms isolated are similar to those seen in the perianal infections of nonimmunosuppressed patients. Despite steroid use, granulocytopenia does not exclude the possible presence of purulent collections, and clinical examination should guide the decision for surgical drainage. In general, perianal wound healing is not prolonged in BMT patients.

Local recurrence in breast cancer: Implications for systemic disease

AbstractBackground: Recurrence in breast carcinoma follows a pattern of growth marked by local, regional, or widespread dissemination. Local recurrence may be the harbinger of systemic disease or failure of local control. Delineation of these processes may have implications in treatment. Methods: A retrospective review found 1,171 patients with stages I and II breast cancer from 1978 to 1990 treated at the City of Hope Medical Center. Results: Twenty-seven percent (n=313) of patients developed recurrences. These were classified as local, including chest wall and regional nodes (n=40), local and distant (n=63), and distant (n=210). Mean follow-up was 60 months. Multivariate analysis demonstrates tumor size was not different between the three groups, but the presence of positive lymph nodes was: local=51%, local and distant=78%, and distant=64%. The disease-free interval was longest in the local group (42 months) versus the local and distant group (23 months) and distant group (39 months). Median survival was calculated from the time of recurrence: local=90 months, local and distant=26 months, and distant=16 months. Conclusions: A group of patients with local recurrence have improved survival and do not develop distant disease. This group may benefit from aggressive surgical treatment to control local disease. These data suggest that a subset of breast tumors can act locally aggressive without metastatic potential.

Impact of a full-time preceptor on the institutional outcome of laparoscopic colectomy

BackgroundLaparoscopic assisted colectomy (LAC) is a difficult operation with long learning curves and conversion rates inversely proportional to the surgeon’s experience. Methods to help train surgeons outside of residency or fellowship programs have been poorly analyzed. This study was undertaken to assess the impact of an experienced laparoscopic surgeon preceptor on the outcome of LAC in a single institutionMethodsIn September 2004, a fellowship-trained laparoscopic surgeon joined our department of surgery. This surgeon served as a LAC preceptor for six inexperienced staff surgeons and four surgical oncology fellows. Clinical and pathologic data from all attempted LAC for the 22 months preceding the arrival of the trained laparoscopic surgeon were compared with those for the 18 months following the recruitment.ResultsBefore the addition of the expert surgeon, 28 LAC were performed in our institution, compared with 63 during the preceptor program. These represented 59% and 95% of eligible operations for each time period, respectively (P = 0.005). Overall conversion rates before and after the preceptor’s arrival decreased from 44% to 14%, respectively (P < 0.05). The chances of conversion were strongly affected by the presence or absence of the preceptor in the operating room (7% vs. 30%, respectively, P = 0.003). Overall complication rates, hospital stay, blood loss, operative time and number of lymph nodes retrieved were not affected by the presence of the preceptor. Operations completed laparoscopically resulted in significantly lower blood loss and length of stay compared with converted ones.ConclusionsA shared departmental preceptor can positively affect the institutional outcome of laparoscopic colectomy. This model may help improve training and patient care in inexperienced centers.

Original ContributionsVisceral Varicella-Zoster after bone marrow transplantation: report of a case series and review of the literature

Objectives: Infection with varicella-zoster virus after bone marrow transplantation (BMT) is a common cause of morbidity and mortality. Visceral involvement with varicella-zoster may be incorrectly ascribed to graft-versus-host disease, resulting in delayed diagnosis and misguided therapy. Methods: A 4-yr retrospective chart review was performed to determine the presenting symptoms and clinical outcome of visceral varicella-zoster virus infection in BMT recipients. Results: Ten BMT recipients who subsequently developed visceral varicella-zoster virus infection were identified. The mean age at diagnosis was 40 yr (range 27–56 yr). Primary hematological malignancies were leukemia (N = 7), myelodysplasia (N = 2), and myelofibrosis (N = 1). Bone marrow transplants in affected patients were autologous (N = 2), related allogeneic (N = 5), or matched unrelated allogeneic (N = 3). The mean time interval from BMT to symptomatic visceral varicella-zoster virus infection was 153 days (range 60–280 days). Presenting symptoms included abdominal pain in all patients, nausea (60%), fever > 38°C (60%), vomiting (50%), pneumonitis (50%), skin rash (40%), and diarrhea (30%). All patients had moderately or profoundly elevated aminotransferases and most had elevated pancreatic enzymes (80%). The mean time interval from the development of abdominal pain to the characteristic skin rash and then diagnosis was 6 and 7 days, respectively (range 4–10 and 4–14 days). Active graft-versus-host disease had previously been documented in five of the eight allogeneic BMT recipients. Immunosuppressive medications were increased at the onset of the abdominal pain in seven of these eight patients for suspected exacerbation of graft-versus-host disease. After recognition of varicella infection, antiviral therapy was promptly initiated; despite this, mortality was still 50%. Conclusions: Visceral involvement with varicella-zoster virus infection can occur as a late complication after both allogeneic and autologous BMT. In these cases, symptoms of severe abdominal pain with associated nausea, vomiting, and diarrhea and elevated liver and pancreatic enzymes preceded the vesicular skin eruption and were confused with graft-versus-host disease. With the increasing application of high-dose chemotherapy followed by stem cell rescue for both hematological and solid tumors, clinicians should be aware of this potentially treatable and often lethal complication.

Evaluation of Expert Criteria for Preoperative Magnetic Resonance Imaging of Newly Diagnosed Breast Cancer

Despite 2 randomized trials reporting no reduction in operations or local recurrence at 1 year, preoperative magnetic resonance imaging (MRI) is increasingly used in diagnostic workup of breast cancer. We evaluated 5 utilization criteria recently proposed by experts. Of women (n = 340) newly diagnosed with unilateral breast cancer who underwent bilateral MRI, most (69.4%) met at least 1 criterion before MRI: mammographic density (44.4%), under consideration for partial breast irradiation (PBI) (19.7%), genetic-familial risk (12.9%), invasive lobular carcinoma (11.8%), and multifocal/multicentric disease (10.6%). MRI detected occult malignant lesion or extension of index lesion in 21.2% of index, 3.3% of contralateral, breasts. No expert criterion was associated with MRI-detected malignant lesion, which associated instead with pre-MRI plan of lumpectomy without PBI (48.2% of subjects): Odds Ratio 3.05, 95% CI 1.57-5.91 (p adjusted for multiple hypothesis testing = 0.007, adjusted for index-vs-contralateral breast and covariates). The expert guidelines were not confirmed by clinical evidence.

Association of Fluid Administration With Morbidity in Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy

Importance Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal cancers can be associated with significant complications. Randomized trials have demonstrated increased morbidity with liberal fluid regimens in abdominal surgery. Objective To investigate the association of intraoperative fluid administration and morbidity in patients undergoing CRS/HIPEC. Design, Setting, and Participants A retrospective analysis of information from a prospectively collected institutional database was conducted at a National Cancer Institute–designated comprehensive cancer center. A total of 133 patients from April 15, 2009, to June 23, 2016, with primary or secondary peritoneal cancers were included. Exposures Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. Main Outcomes and Measures Morbidity associated with intraoperative fluid management calculated by the comprehensive complication index, which uses a formula combining all perioperative complications and their severities into a continuous variable from 0 to 100 in each patient. Results Of the 133 patients identified, 38% and 37% had diagnoses of metastatic appendiceal and colorectal cancers, respectively. Mean age was 54 (interquartile range [IQR], 47-64) years, and mean peritoneal cancer index was 13 (IQR, 7-18). Mitomycin and platinum-based chemotherapeutic agents were used in 96 (72.2%) and 37 (27.8%) of the patients, respectively. Mean intraoperative fluid (IOF) rate was 15.7 (IQR, 11.3-18.7) mL/kg/h. Mean comprehensive complication index (CCI) was 26.0 (IQR, 8.7-36.2). On multivariate analysis, age (coefficient, 0.32; 95% CI, 0.01-0.64; P = .04), IOF rate (coefficient, 0.97; 95% CI, 0.19-1.75; P = .02), and estimated blood loss (coefficient, 0.02; 95% CI, 0.01-0.03; P = .002) were independent predictors of increased CCI. In particular, patients who received greater than the mean IOF rate experienced a 43% increase in the CCI compared with patients who received less than the mean IOF rate (31.5 vs 22.0; P = .02). Conclusions and Relevance Intraoperative fluid administration is associated with a significant increase in perioperative morbidity in patients undergoing CRS/HIPEC. Fluid administration protocols that include standardized restrictive fluid rates can potentially help to mitigate morbidity in patients undergoing CRS/HIPEC.