Household catastrophic health expenditure for COVID-19 during March-August 2021, in South India: a cross-sectional study.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic increased the utilisation of healthcare services. Such utilization could lead to higher out-of-pocket expenditure (OOPE) and catastrophic health expenditures (CHE). We estimated OOPE and the proportion of households that experienced CHE by conducting a cross-sectional survey of 1200 randomly selected confirmed COVID-19 cases. METHODS: A cross-sectional survey was conducted by telephonic interviews of 1200 randomly selected COVID-19 patients who tested positive between 1 March and 31 August 2021. We collected household-level information on demographics, income, expenditure, insurance coverage, direct medical and non-medical costs incurred toward COVID-19 management. We estimated the proportion of CHE with a 95% confidence interval. We examined the association of household characteristics; COVID-19 cases, severity, and hospitalisation status with CHE. A multivariable logistic regression analysis was conducted to ascertain the effects of variables of interest on the likelihood that households face CHE due to COVID-19. RESULTS: The mean (95%CI) OOPE per household was INR 122,221 (92,744-1,51,698) [US$1,643 (1,247-2,040)]. Among households, 61.7% faced OOPE, and 25.8% experienced CHE due to COVID-19. The odds of facing CHE were high among the households; with a family member over 65 years [OR = 2.89 (2.03-4.12)], with a comorbid individual [OR = 3.38 (2.41-4.75)], in the lowest income quintile [OR = 1.82 (1.12-2.95)], any member visited private hospital [OR = 11.85 (7.68-18.27)]. The odds of having CHE in a household who have received insurance claims [OR = 5.8 (2.81- 11.97)] were high. Households with one and more than one severe COVID-19 increased the risk of CHE by more than two-times and three-times respectively [AOR = 2.67 (1.27-5.58); AOR = 3.18 (1.49-6.81)]. CONCLUSION: COVID-19 severity increases household OOPE and CHE. Strengthening the public healthcare and health insurance with higher health financing is indispensable for financial risk protection of households with severe COVID-19 from CHE.

Differential responses of sorghum genotypes to drought stress revealed by physio-chemical and transcriptional analysis.

Sorghum is an essential food crop for millions of people in the semi-arid regions of the world, where its production is severely limited by drought stress. Drought in the early stages of crop growth and development irreversibly interferes, which leads to poor yield. The effect of drought stress in sorghum was studied at physiological, biochemical, and molecular levels in a set of two genotypes differing in their tolerance to drought. Drought stress was imposed by restraining water for 10 days on 25 days old seedlings. A significant influence of water stress was observed on the considered morpho-physiological and biochemical traits. The genotype DRT1019 exhibited physiological and biochemical indicators of drought avoidance through delayed leaf rolling, osmotic adjustment, ideal gas-exchange system, solute accumulation, an increased level of enzyme synthesis and root trait expression as compared to the ICSV95022 genotype. Furthermore, differences in the metabolite changes viz. total carbohydrate, total amides, and lipids were found between the two genotypes under drought stress. In addition, transcript profiling of potential candidate drought genes such as SbTIP3-1, SbDHN1, SbTPS, and SbDREB1A revealed up-regulation in DRT1019, which corresponded with other important physiological and biochemical parameters exhibited in the genotype. In conclusion, this study provides an improved understanding of whole plant response to drought stress in sorghum. Additionally, our results provide promising candidate genes for drought tolerance in sorghum that can be used as potential markers for drought tolerance breeding programs.

Manipulating the expression of chemokine receptors enhances delivery and activity of cytokine-induced killer cells.

BACKGROUND: Cytokine-induced killer (CIK) cells are ex vivo-expanded immune cells that express NK-cell and T-cell markers and that are routinely used in the treatment of many cancers. One key advantage of CIK cells is their ability to efficiently traffic to many solid tumours. Although likely to be mediated by chemokine receptor (CKR) expression, a thorough examination of the mechanism of tumour targeting has not been previously explored. METHODS: Here, human CIK cell expansions were examined for the level, profile and kinetics of CKR expression. RESULTS: It was found that CIK cells express a panel of CKRs, with considerable variation between donors. Importantly, CKR levels dropped considerably beyond 14 days in culture, being significantly reduced by day 28 (the time at which cytolytic activity peaked). As such, CIK preparations that are used clinically may not have optimal CKR expression. Several approaches were found to re-stimulate CKR cell-surface levels at these later time points. These approaches also enhanced cytolytic activity in vitro and were demonstrated to increase both in vivo tumour trafficking and anti-tumour activity in mouse models. CONCLUSIONS: Simple modifications of the CIK expansion protocol could therefore be used to significantly enhance the anti-tumour effects of this therapy.

Contribution of infection and vaccination to population-level seroprevalence through two COVID waves in Tamil Nadu, India.

This study employs repeated, large panels of serological surveys to document rapid and substantial waning of SARS-CoV-2 antibodies at the population level and to calculate the extent to which infection and vaccination separately contribute to seroprevalence estimates. Four rounds of serological surveys were conducted, spanning two COVID waves (October 2020 and April-May 2021), in Tamil Nadu (population 72 million) state in India. Each round included representative populations in each district of the state, totaling ≥ 20,000 persons per round. State-level seroprevalence was 31.5% in round 1 (October-November 2020), after India's first COVID wave. Seroprevalence fell to 22.9% in round 2 (April 2021), a roughly one-third decline in 6 months, consistent with dramatic waning of SARS-Cov-2 antibodies from natural infection. Seroprevalence rose to 67.1% by round 3 (June-July 2021), with infections from the Delta-variant induced second COVID wave accounting for 74% of the increase. Seroprevalence rose to 93.1% by round 4 (December 2021-January 2022), with vaccinations accounting for 63% of the increase. Antibodies also appear to wane after vaccination. Seroprevalence in urban areas was higher than in rural areas, but the gap shrunk over time (35.7 v. 25.7% in round 1, 89.8% v. 91.4% in round 4) as the epidemic spread even in low-density rural areas.

Potential for enhanced therapeutic activity of biological cancer therapies with doxycycline combination.

Despite significant strides made in the clinical translation of adoptive immune cell therapies, it is apparent that many tumors incorporate strategies to avoid recognition by receptors expressed on the immune cells, such as NKG2D. Strategies that stabilize the expression of ligands for these receptors may enhance the therapeutic potential of these and related therapies. Doxycycline inhibits matrix metalloproteinases (MMPs) that act to cleave the extracellular domain of MICA/B, ligands for the NKG2D receptor. Doxycycline treatment blocked shedding of MICA/B from a panel of human tumor cells, but also acted to increase their expression and cell surface translocation, possibly through its action on ATM. This meant that many tumor cells displayed increased MICA/B expression and enhanced susceptibility to CIK cells. Interestingly, doxycycline also selectively enhanced the replication of oncolytic vaccinia in many tumor cell lines, leading to increased sensitivity to these therapies. Combination (CIK-oncolytic vaccinia) therapies used in conjunction with doxycycline led to increased anti-tumor effects. The unexpected and pleiotropic beneficial anti-tumor effects of doxycycline on both immune cell and oncolytic viral therapies make it an excellent candidate for rapid clinical testing.

Assessment of Registry-Based Surveillance Statistics Used for Cancer Control in the Dindigul District in South India.

Background: Cancer incidence rates from the Dindigul district were lower by 50% than Chennai in Tamil Nadu for most cancers. This study describes the cancer surveillance statistics and provides an assessment of missing cases from routine registration in the Dindigul Ambilikkai Cancer Registry (DACR), covering a predominantly rural population in the Dindigul district. Method: A total of 21,214 incident cancers in the DACR during 2003-2017 were examined for this study. Cancer registration was carried out by active case-finding following standard international norms. A total of 12,541 incident cancers registered during 2003-2012 and followed through 2014 were used to estimate survival. Data on follow-up were obtained through a mixture of active and passive methods. Survival probability was estimated by actuarial methods. A random survey carried out independently was used to assess the quality of case ascertainment. Results: The age-standardized rate (ASR) per 100,000 population was higher among women (76.2) than men (61) in 2013-2017, with both sexes reporting a 17% increase compared to 2003-2007. The most common cancers were cervix (ASR,18.5) and female breast (ASR,17.1), with percentage changes of -19% and +46.1%, respectively. Lung cancer (ASR, 5.5) was top among men with an increasing trend (+57.1%). The percent change in ASR of mouth cancer showed opposite trends among men (+24.3%) and women (- 21.4%). The ASR of colorectal cancers almost doubled among men between 2003-2007 and 2013-2017 (3.9; +94.7%). The 5- and 10-year absolute survival for all cancers were 31% and 20%, respectively. Out of 365 incident cancers that occurred during 2003-2010 in the surveyed areas, 310 (84.9%) were already registered in the DACR, while 55 were newly identified from the survey (15.1%). Inadequate coverage of sources outside the Dindigul district was significant (P = .002), with the highest number of missed cases from hospitals under nongovernment sectors (58.3%). Underascertainment was higher among cancer patients living in hilly regions (60%) and border areas (47.4%) than in core regions (P = .05). Conclusion: Because of an enacted government order making cancer a notifiable disease, the registry-based cancer surveillance could be extended, covering a population of 80 million in a cost-effective manner with enhanced coverage and systematic evaluation of cancer-screening programs.

Chimeric antigen receptors for treatment of glioblastoma: a practical review of challenges and ways to overcome them.

Glioblastoma (GBM) is by far the most common and the most aggressive of all the primary brain malignancies. No curative therapy exists, and median life expectancy hovers at around 1 year after diagnosis, with a minute fraction surviving beyond 5 years. The difficulty in treating GBM lies in the cancer's protected niche within the blood-brain barrier and the heterogeneity of the cancer cells, which possess varying degrees of susceptibility to various common modalities of treatment. Over time, it is the tumor heterogeneity of GBM and the ability of the cancer stem cells to evolve in response treatment that renders the cancer refractory to conventional treatment. Therefore, research has increasingly focused on treatment that incorporates knowledge of GBM molecular biology to therapeutic strategies. One type of therapy that shows great promise is the area of T-cell immunotherapy to target GBM-specific tumor antigens. One attractive strategy is to use T cells that have undergone genetic modification to express a chimeric antigen receptor capable of interacting with tumor antigens. In this article, we will review chimeric antigen receptor T-cell therapy, their advantages, drawbacks, challenges facing their use and how those challenges may be overcome.

Jarcho's Syndrome: Bone Marrow Infiltrates from a Gastric Malignancy.

Bone and bone marrow metastasis is extremely rare in adenocarcinoma particularly from the stomach. We present a case of gastric carcinoma primarily manifesting as anemia and pancytopenia. On evaluation, he was found to have bone marrow secondaries from a gastric primary tumor. Though such metastasis is rare, patients with refractory anemia must be evaluated to search for solid organ malignancy like the stomach.

O6-benzylguanine potentiates the antitumor effect of locally delivered carmustine against an intracranial rat glioma.

Local delivery of carmustine (BCNU) via biodegradable polymers prolongs survival against experimental brain tumors and in human clinical trials. O6-benzylguanine (O6-BG), a potent inhibitor of the DNA repair protein, O6-alkylguanine-DNA alkyltransferase (AGT), has been shown to reduce nitrosourea resistance and, thus, enhance the efficacy of systemic BCNU therapy in a variety of tumor models. In this report, we demonstrate that O6-BG can potentiate the activity of BCNU delivered intracranially via polymers in rats challenged with a lethal brain tumor. Fischer 344 rats received a lethal intracranial challenge of 100,000 F98 glioma cells (F98 cells have significant AGT activity, 328 fmol/mg protein). Five days later, animals receiving an i.p. injection of O6-BG (50 mg/kg) 2 h prior to BCNU polymer (3.8% BCNU by weight) implantation had significantly improved survival (n = 7; median survival, 34 days) over animals receiving either O6-BG alone (n = 7; median survival, 22 days; P = 0.0002) or BCNU polymer alone (n = 8; median survival, 25 days; P = 0.0001). Median survival for the control group (n = 8) was 23.5 days. Moreover, there was no physical, behavioral, or pathological evidence of treatment-related toxicity. These findings suggest that O6-BG can potentiate the effects of interstitially delivered BCNU and, for tumors expressing significant AGT, may be necessary for the BCNU to provide a meaningful therapeutic benefit. Given the clinical use of BCNU polymers against malignant gliomas, concurrent treatment with O6-BG may provide an important addition to our therapeutic armamentarium.

Paracrine immunotherapy with interleukin-2 and local chemotherapy is synergistic in the treatment of experimental brain tumors.

Potent immune responses against malignant brain tumors can be elicited by paracrine intracranial (i.c.) immunotherapy with interleukin (IL)-2. Additionally, i.c. delivery of carmustine via biodegradable polymers has been shown to significantly prolong survival in both animal models and clinical trials. In this study, we show that the combination of paracrine immunotherapy, with nonreplicating genetically engineered tumor cells that produce IL-2, and local delivery of chemotherapy by biodegradable polymers prolongs survival in a synergistic manner in mice challenged intracranially with a lethal murine brain tumor. Animals receiving IL-2-transduced cells and polymers containing 10% 1,3-bis(2-chloroethyl)-1-nitrosourea had significantly improved survival compared with animals receiving IL-2-transduced cells or 10% 1,3-bis(2-chloroethyl)-1-nitrosourea alone. Median survival for the control group was 19 days. Survival in animals receiving IL-2-transduced cells and 1% carboplatin-containing polymers was also significantly improved compared with either therapy alone. Histopathological examination on day 14 of animals receiving combination treatment showed rare degenerating tumor cells. In addition to tissue necrosis surrounding the polymer, a marked inflammatory reaction was observed. In long-term survivors (all animals receiving combination treatment), no tumor was observed and the inflammatory reaction was completely resolved. The brains of animals receiving combination therapy showed both tissue necrosis due to local chemotherapy and strong inflammation due to paracrine immunotherapy. The demonstration of synergy between paracrine IL-2 and local i.c. delivery of antineoplastic drugs is novel and may provide a combined treatment strategy for use against both primary and metastatic i.c. tumors.

Role of lipid-soluble complexes in targeted tumor therapy.

UNLABELLED: Radionuclide therapy remains a promising arsenal against cancer. However, low tumor uptake, high radiation dose to normal organs, and subsequent adverse effects are challenging problems. This study assessed the therapeutic significance of lipid-soluble compounds of (111)In, which passively diffuse through the cell membrane, bind to cytoplasmic components, and remain cell bound until decay. METHODS: Athymic nude mice bearing human colorectal, prostate, or breast cancer received 11.1-14.8 MBq (300-400 micro Ci) (111)In-8-hydroxyquinoline ((111)In-oxine) or (111)In-mercaptopyridine-N-oxide ((111)In-Merc) in 200 micro L solution intratumorally through a multihole needle. Tumors in some mice were dissected, and 20- micro m-thick sections were autoradiographed. In additional mice, tumor diameter was measured daily, mice were imaged and weighed, and blood samples were drawn for determination of neutrophil counts for up to 28 d after injection. Some mice were sacrificed at predetermined times for quantitative tissue distribution of (111)In. Additionally, tumor cells were labeled with (111)In-oxine and homogenized, and (111)In associated with cell components was determined using polyacrylamide gel electrophoresis. Radiation dose that could be delivered to adjacent tissues was estimated. The (111)In absorbed dose as a function of radial position r in a 1-g tumor was theoretically compared with those of beta-emitting radionuclides (90)Y and (177)Lu. RESULTS: More than 85% of (111)In remained in tumors, bound to cell cytoplasmic components of apparent molecular weights 250 and 6 kDa. (111)In in tumors was uniformly distributed. Only 2% of the injected (111)In was in the liver, kidneys, and carcass. Statistical analysis showed that on day 28, control tumors grew >100%, whereas treated tumors either had growth arrest or grew only slowly (17%). The estimated radiation dose per megabecquerel (millicurie) injected was 90 Gy/g (9,000 rad/g), of which 64% was from conversion electrons, 16% from Auger electrons, 20% from gamma-photons and x-rays, respectively. Radiation dose to adjacent normal organs was 5%-10% of the radiation dose to the tumor and negligible to the liver and kidneys. Neutrophil counts remained unchanged. Mouse body weight was +/-10% of the initial weight. The radiation dosimetry for (111)In and (177)Lu compared favorably, but not that of (90)Y. CONCLUSION: Treatment is independent of receptor density, heterogeneity, or the hypoxic status of cells. It is applicable to treat all known and accessible tumor types, and it delivers a negligible radiation dose to vital organs and only 5%-10% of the radiation dose to organs adjacent to the tumor. Intratumoral administration of (111)In-oxine appears to be a feasible, effective, safe, and promising treatment for cancer.

Nerve injury associated with laparoscopic inguinal herniorrhaphy.

BACKGROUND: As laparoscopic herniorrhaphy becomes more popular, it is important to realize the potential for injury to surrounding neural structures, with attendant severe disability. METHODS: Herein are discussed two patients with disabling neuralgia after laparoscopic herniorrhaphy. RESULTS: Both patients were treated with transabdominal removal of their prosthetic materials and anchoring staples, with dramatic symptomatic improvement. CONCLUSIONS: The surgeon should be aware of the anatomic considerations accompanying laparoscopic herniorrhaphy. In regard to nerve injury, laparoscopic herniorrhaphy may pose certain disadvantages over traditional hernia repairs. It may diminish the ability to appreciate the course of nerves in the inguinal region and their relationship to the spermatic cord, and injury to nerves may be difficult to recognize and treat.

Implantable Slow-Release Chemotherapeutic Polymers for the Treatment of Malignant Brain Tumors.

BACKGROUND: Despite significant advances in neurosurgery, radiation therapy, and chemotherapy, the prognosis for patients with malignant brain tumors remains dismal. In an effort to improve control of local disease, we have developed a biodegradable, controlled-release polymer that is implanted directly at the tumor site. METHODS: The preclinical and clinical development of the polymeric delivery of chemotherapeutic agents for treatment of patients with malignant gliomas is reviewed. RESULTS: Carmustine (BCNU)-impregnated biodegradable polymer is the first new therapy approved by the FDA for patients with gliomas in 23 years. This delivery system provides high local concentration of drug with minimal systemic toxicity and obviates the need for drug to cross the blood-brain barrier. Randomized, multi-institutional, double-blinded, placebo-controlled studies have shown improved survival in patients treated for gliomas both at initial presentation and at recurrence. Several clinical principles have emerged from the use of this polymer system, and further applications are currently being investigated. CONCLUSIONS: Local delivery of therapeutic agents via biodegradable polymers may play an increasing role in patients with brain tumors.

The Hunterian Neurosurgical Laboratory: the first 100 years of neurosurgical research.

Modern neurosurgery has long had a strong laboratory foundation, and much of this tradition can be traced to the Hunterian Neurosurgical Laboratory of the Johns Hopkins Hospital. Founded with the basic goals of investigating the causes and symptoms of disease and establishing the crucial role that surgeons may play in the treatment of disease, the Hunterian laboratory has adhered to these tenets, despite the dramatic changes in neurosurgery that have occurred in the last 100 years. Named for the famous English surgeon John Hunter (1728-1793), the Hunterian laboratory was conceived by William Welch and William Halsted as a special laboratory for experimental work in surgery and pathology. In 1904, Harvey Cushing was appointed by Halsted to direct the laboratory. With the three primary goals of student education, veterinary surgery that stressed surgical techniques, and meticulous surgical and laboratory record-keeping, the laboratory was quite productive, introducing the use of physiological saline solutions, describing the anatomic features and function of the pituitary gland, and establishing the field of endocrinology. In addition, the original development of hanging drop tissue culture, fundamental investigations into cerebrospinal fluid, and countless contributions to otolaryngology by Samuel Crowe all occurred during this "crucible" period. In 1912, Cushing was succeeded by Walter Dandy, whose work on experimental hydrocephalus and cerebrospinal fluid circulation led to the development of pneumoencephalography. The early days of neurosurgery evolved with close ties to general surgery, and so did the Hunterian laboratory. After Dandy began devoting his time to clinical work, general surgeons (first Jay McLean and then, in 1922, Ferdinand Lee) became the directors of the laboratory. Between 1928 and 1942, more than 150 original articles were issued from the Hunterian laboratory; these articles described significant advances in surgery, including pioneering research on calcium metabolism by William MacCallum and Carl Voegtlin and seminal preclinical work by Alfred Blalock and Vivian Thomas that led to the famous "blue baby" operation in 1944. With the introduction of the operating microscope in the 1950s, much of the focus in neurosurgical science shifted from the laboratory to the operating room. The old Hunterian building was demolished in 1956. The Hunterian laboratory for surgical and pathological research was rebuilt on its original site in 1987, and the Hunterian Neurosurgical Laboratory was reestablished in 1991, with a focus on novel treatments for brain tumors. The strong tradition of performing basic research with clinical relevance has continued.

Combined anterior craniofacial resection for tumors involving the cribriform plate: early postoperative complications and technical considerations.

OBJECTIVE: Combined craniofacial resection has become the standard approach for malignant tumors involving the cribriform plate and anterior cranial fossa. Despite its widespread application, however, many surgeons agree that the procedure carries a risk of significant morbidity and even mortality. The purpose of this study was to analyze the experience at a single institution to determine the incidence of early postoperative complications encountered after combined craniofacial resection of tumors involving the cribriform plate and to provide information to improve management. METHODS: Between 1987 and 1997, 168 patients underwent combined craniofacial resection at the National Cancer Institute of Milan for tumors involving the cribriform plate. Patient charts, operative notes, follow-up clinic notes, radiographic studies, and pathology reports were analyzed. Morbidity encountered in the first 30 cases was compared with that encountered in the subsequent 138 cases. RESULTS: The most frequently encountered pathological findings were adenocarcinoma (53.6%), squamous cell carcinoma (17%), and esthesioneuroblastoma (9.8%). Eight patients (4.7%) died, 6 of whom were among the first 30 patients to undergo resection. Among patients with fatal complications were three with meningoencephalitis, three with intracranial hemorrhage, and one with myocardial infarction. Fifty patients (29.7%) had nonfatal morbidity; 16 of these patients were among the first 30 patients operated. Transient cerebrospinal fluid leakage was the most frequent adverse effect (9.5%); 12 patients (7.1%) had pneumocephalus, 3 (1.8%) had meningitis, 4 (2.4%) had wound infections, 3 (1.8%) experienced transient impairment of mental status, 3 (1.8%) had transient diplopia, 2 (1.2%) had diabetes insipidus, and 1 (0.6%) had bone flap necrosis. CONCLUSION: We observed a dramatic decrease in mortality and morbidity in patients who underwent combined craniofacial resection after the first 30 cases in our series. Improvement of specific aspects of surgical technique, such as more refined reconstructive methods and improved prophylactic antibiotic therapy, is at least partly responsible for this favorable trend.

Long-term visual outcome after nonradical microsurgery patients with parasellar and cavernous sinus meningiomas.

OBJECTIVE: To determine the long-term visual outcome in patients with parasellar and cavernous sinus meningiomas treated with nonradical surgery. METHODS: Retrospective clinical review of 29 patients with parasellar or cavernous sinus meningiomas and visual sensory or ocular motor dysfunction at presentation, all of whom had at least 10 years of follow-up after initial diagnosis and treatment with nonradical surgery. RESULTS: Nineteen of 29 patients had a unilateral or bilateral optic neuropathy at presentation, and 7 patients developed a unilateral or bilateral optic neuropathy during a mean follow-up period of 13.6 years. However, 27 (93%) of 29 patients retained vision of 20/40 or better in at least one eye, and 14 patients (48%) retained vision of 20/40 or better in both eyes. New ocular motility deficits developed in 3 (10%) of 29 patients during the follow-up period. CONCLUSION: Radical surgery is not required to achieve long-term useful visual function for patients with parasellar or cavernous sinus meningiomas.

Local delivery of chemotherapy prolongs survival in experimental brain metastases from breast carcinoma.

OBJECTIVE: Despite improved systemic control of metastatic breast cancer, the incidence of brain metastases from breast carcinoma continues to rise, in part because most systemically administered agents have poor central nervous system penetration. Therefore, as a method of optimizing drug delivery into the central nervous system, we studied the safety and efficacy of chemotherapy delivered locally via biodegradable polymers in a mouse model of breast carcinoma metastases to the brain. METHODS: The chemotherapeutic agents carmustine (BCNU), carboplatin, and camptothecin were incorporated into controlled release polymers and tested individually against intracranial challenges of EMT-6 breast tumor in BALB/c female mice. For each drug, four groups were tested: Group 1, empty polymer (no drug); Group 2, external beam radiotherapy (XRT) alone; Group 3, local chemotherapy from biodegradable polymer alone; and Group 4, local chemotherapy and XRT together. Polymers were implanted 5 days after intracranial tumor inoculation; XRT was administered on Days 7 through 9 (300 cGy/d). RESULTS: BCNU polymer alone (n = 10; median survival time, >200 d; P < 0.0001) and BCNU and XRT together (n = 10; median survival time, 41 d; P = 0.02) significantly improved survival in mice with intracranial EMT-6 breast cancer in comparison with control animals (n = 20; median survival time, 17 d). Carboplatin and camptothecin, either with or without XRT, and XRT alone did not have any significant effect on survival. CONCLUSION: Local delivery of BCNU with biodegradable polymers can significantly prolong survival in a murine model of intracranial metastatic breast cancer. Surgical resection and placement of BCNU polymers into the resection cavity may decrease the incidence of local recurrence of breast cancer metastases with minimal morbidity.

Microanatomical variations in the cerebellopontine angle associated with vestibular schwannomas (acoustic neuromas): a retrospective study of 1006 consecutive cases.

OBJECT: Great advances in neuroimaging, intraoperative cranial nerve monitoring, and microsurgical technique have shifted the focus of acoustic neuroma surgery from prolonging life to preserving cranial nerve function in patients. An appreciation of the vascular and cranial nerve microanatomy and the intimate relationship between neurovascular structures and the tumor is essential to achieve optimum results. In this paper the authors analyze the microanatomical variations in location of the facial and cochlear nerves in the cerebellopontine angle (CPA) associated with acoustic neuromas and, additionally, describe the frequency of involvement of surrounding neural and vascular structures with acoustic tumors of varying size. The authors base these findings on their experience with 1006 consecutive patients who underwent surgery via a retrosigmoid or translabyrinthine approach. METHODS: Between July 1969 and January 1998, the senior author (D.M.L.) performed surgery in 1022 patients for acoustic neuroma: 705 (69%) via the retrosigmoid (suboccipital); 301 (29%) via the translabyrinthine; and 16 (2%) via the middle fossa approach. Patients undergoing the middle fossa approach were excluded from the study. The remaining 1006 patients were subdivided into three groups based on tumor size: Group I tumors (609 patients [61%]) were smaller than 2.5 cm; Group II tumors (244 patients [24%]) were between 2.5 and 4 cm; and Group III tumors (153 patients [15%]) were larger than 4 cm. The senior author's operative notes were analyzed for each patient. Relevant cranial nerve and vascular "involvement" as well as anatomical location with respect to the tumor in the CPA were noted. "Involvement" was defined as adherence between neurovascular structure and tumor (or capsule), for which surgical dissection was required to free the structure. Seventh and eighth cranial nerve involvement was divided into anterior, posterior, and polar (around the upper or lower pole) locations. Anterior and posterior locations were further subdivided into upper, middle, or lower thirds of the tumor. The most common location of the seventh cranial nerve (facial) was the anterior middle third of the tumor for all groups, although a significant number were found on the anterior superior portion. The posterior location was exceedingly rare (< 1%). Interestingly, patients with smaller tumors (Group I) had an incidence (3.4%) of the seventh cranial nerve passing through the tumor itself, equal to that of patients with larger tumors. The most common location of the eighth cranial nerve complex was the anterior inferior portion of the tumor. Not surprisingly, larger tumors (Group III) had a higher incidence of involvement of fourth cranial nerve (41%), fifth cranial nerve (100%), ninth-11th cranial nerve complex (99%), and 12th cranial nerve (31%), as well as superior cerebellar artery (79%), anterior inferior cerebellar artery (AICA) trunk (91.5%), AICA branches (100%), posterior inferior cerebellar artery (PICA) trunk (59.5%), PICA branches (79%), and the vertebral artery (VA) (93.5%). A small number of patients in Group III also had AICA (3.3%), PICA (3.3%), or VA (1.3%) vessels within the tumor itself. CONCLUSIONS: In this study, the authors show the great variation in anatomical location and involvement of neurovascular structures in the CPA. With this knowledge, they present certain technical lessons that may be useful in preserving nerve function during surgery and, in doing so, hope to provide neurosurgeons and neurootologists with valuable information that may help to achieve optimum outcomes in patients.