An evidence-based treatment algorithm for colorectal polyp cancers: results from the Scottish Screen-detected Polyp Cancer Study (SSPoCS).

OBJECTIVES: Colorectal polyp cancers present clinicians with a treatment dilemma. Decisions regarding whether to offer segmental resection or endoscopic surveillance are often taken without reference to good quality evidence. The aim of this study was to develop a treatment algorithm for patients with screen-detected polyp cancers. DESIGN: This national cohort study included all patients with a polyp cancer identified through the Scottish Bowel Screening Programme between 2000 and 2012. Multivariate regression analysis was used to assess the impact of clinical, endoscopic and pathological variables on the rate of adverse events (residual tumour in patients undergoing segmental resection or cancer-related death or disease recurrence in any patient). These data were used to develop a clinically relevant treatment algorithm. RESULTS: 485 patients with polyp cancers were included. 186/485 (38%) underwent segmental resection and residual tumour was identified in 41/186 (22%). The only factor associated with an increased risk of residual tumour in the bowel wall was incomplete excision of the original polyp (OR 5.61, p=0.001), while only lymphovascular invasion was associated with an increased risk of lymph node metastases (OR 5.95, p=0.002). When patients undergoing segmental resection or endoscopic surveillance were considered together, the risk of adverse events was significantly higher in patients with incomplete excision (OR 10.23, p<0.001) or lymphovascular invasion (OR 2.65, p=0.023). CONCLUSION: A policy of surveillance is adequate for the majority of patients with screen-detected colorectal polyp cancers. Consideration of segmental resection should be reserved for those with incomplete excision or evidence of lymphovascular invasion.

Chicken or the leg: Sigmoid colon perforation by ingested poultry fibula proximal to an occult malignancy.

INTRODUCTION: Colonic perforation by ingested foreign bodies is exceedingly rare, with the diagnosis made more challenging by patients infrequently recalling any inadvertent ingestion and the poor sensitivity of plain radiography. PRESENTATION OF CASE: The presented case demonstrates that bony perforation of the large bowel might occur immediately proximal to an otherwise occult colonic malignancy. DISCUSSION: Ingestion of foreign bodies is common and rarely results in colonic perforation. However, bony ingestion is not usually remembered and can be missed even with cross-sectional imaging. If present, consideration should be given to the presence of an adjacent concealed colon cancer. CONCLUSION: The co-existence of separate pathology should be carefully assessed in these patients, since this has important implications for relevant investigations and appropriate surgical management.

Meningiomas of the cerebellopontine angle.

BACKGROUND: Meningiomas of the cerebellopontine angle (CPA), although uniform in location, are diverse with regard to the site of dural origin and displacement of neurovascular structures. A study of patients with CPA meningiomas was undertaken to gain more information regarding the relationship between site of dural attachment, clinical presentation, operative approach, and outcome. METHODS: In this report, we retrospectively review 40 patients with CPA meningiomas managed surgically. RESULTS: Common clinical presentations were hearing loss, unsteadiness, and dysequilibrium. Findings upon physical examination included hearing loss (73%), cerebellar signs (32%), trigeminal neuropathy (16%), and facial nerve dysfunction (16%). The most common site of dural origin was the petrous ridge (anterior to the IAC [26%], posterior [21%], superior [18%], and inferior [16%]). Less common sites of dural origin included the tentorium (31%), the clivus (15%), the IAC (10%), and the jugular foramen (8%). Site of dural origin determined the direction of displacement of the facial/vestibulocochlear nerve bundle. The most common microsurgical complication was facial nerve dysfunction (30%). Gross total resection was achieved in 82% of cases, whereas 18% underwent subtotal resection. Two patients died. Follow-up ranged from three months to 13 years with three recurrences. CONCLUSIONS: CPA meningiomas displace the seventh and eighth cranial nerves in various directions depending on the site of dural origin. Total surgical excision can be accomplished in the majority of cases with acceptable morbidity.

Temporal bone meningiomas.

Meningiomas involving the temporal bone may originate from arachnoid cell nests present within the temporal bone (intratemporal), but more frequently originate from arachnoid cell nests of the posterior or middle cranial fossa with secondary invasion of the TB (extratemporal). In this study, we retrospectively reviewed the charts of 13 patients with meningiomas involving the temporal bone who underwent surgery. Tumors of the posterior fossa with only temporal bone hyperostosis, but without invasion, were excluded. Patients presented primarily with otologic symptoms and signs. The tumors originated in the temporal bone (5/13), jugular foramen (4/13), petroclival region (2/13), the asterion (1/13) or the internal auditory meatus (1/13). All of the intratemporal meningiomas had the radiological appearance of en-plaque menigiomas. The tumor extended into the middle ear (11/13), eustachian tube (5/13), and/or the labyrinth (3/13). A gross total resection was achieved in 11 patients and a subtotal resection in 2 patients. The lower cranial nerves were infiltrated by tumor in 4 patients, and were sacrificed. At a mean follow-up of approximately 6 years, 12 patients are currently alive and doing well and 1 died from tumor progression. Six patients showed tumor recurrence and were reoperated on (5/6) or followed conservatively (1/6). Surgical treatment of temporal bone meningiomas is associated with high recurrence rate due to indiscreet tumor margins. Combined surgical approaches (temporal craniotomy and mastoidectomy) by neurosurgical and otological teams are recommended for meningiomas originating in the temporal bone.

Asterion meningiomas.

Asterion meningiomas arise from the posterior petrous ridge at the junction of the transverse and sigmoid sinuses (sinodural angle). The authors retrospectively reviewed the charts of seven patients with asterion meningiomas who underwent a Simpson I tumor resection by either the petrosal or suboccipital approach. Patients presented with headaches, dizziness, ataxia, or seizures. Preoperative angiograms and intraoperative observations confirmed occlusion of the transverse and sigmoid sinuses by tumor, thrombus, or both in four of the patients. In all cases, tumor infiltrated the sinuses and the sinuses were ligated without adverse sequelae. Temporal bone invasion was seen in one patient who had the only tumor recurrence. Postoperatively, there were two transient CSF leaks. Asterion meningiomas can be completely resected with a low incidence of major morbidity. In this small series, a patent transverse/sigmoid sinus was resected in three patients without sequelae. We believe that in young patients with asterion meningiomas a nondominant transverse/sigmoid sinus should be resected if the torcula is patent. More research is needed to determine the safety of resecting a patent dominant transverse/sigmoid sinus.

Use of cranial surface anatomic fiducials for interactive image-guided navigation in the temporal bone: a cadaveric study.

OBJECTIVE: Because of the intricate anatomy of the temporal bone, we examined the feasibility and reliability of cranial surface anatomic fiducials to register computed tomographic images of the temporal bone by using a frameless image-guided system. METHODS: One-millimeter thick computed tomographic slices and the smallest possible field of view were used to register 10 dry and 10 fresh temporal bones from cadavers. The fiducials used for registration included the umbo of the tympanic membrane, emissary foramina, the asterion, various sutures, the tip of the mastoid process, and Henle's spine. RESULTS: Mean initial fiducial registration error ranged from 0.6 to 0.7 mm, and was reduced to 0.5 and 0.4 mm for the dry cranial and cadaveric studies, respectively, by eliminating or reregistering inexact fiducials. Mean target localization error ranged from 0.91 to 2.44 mm for superficial structures of the temporal bone in the dry cranial specimens and from 0.71 to 1.52 mm for deep structures such as the facial nerve, semicircular canals and ossicles in the cadaveric study. CONCLUSION: Interactive image-guided navigation in the temporal bone is possible with registration of cranial surface anatomic fiducials. It may be useful to the neurosurgeon and otologist in identifying critical anatomic structures of the temporal bone encountered during the translabyrinthine, retrolabyrinthine presigmoid, and suboccipital approaches.

Image-interactive orientation in the middle cranial fossa approach to the internal auditory canal: an experimental study.

Approaches through the middle cranial fossa directed at reaching the internal auditory canal (IAC) invariably employ exposure of the geniculate ganglion, the superior semicircular canal (SSC) or the epitympanum. This involves risk to the facial nerve and hearing apparatus. To minimize this risk, we conducted a laboratory study on 9 cadaver temporal bones by using an image-interactive guidance system (StealthStation) to provide topographic orientation in the middle fossa approach. Surface anatomic fiducials such as the umbo of the tympanic membrane, Henle's spine, the root of the zygoma and various sutures were used as fiducials for registration of CT-images of the temporal bone. Accurate localization of the IAC was achieved in every specimen. Mean target localization error varied from 1.20 to 1.38 mm for critical structures in the temporal bone such as the apex of the cochlea, crus commune, ampula of the SSC and facial hiatus. Our results suggest that frameless stereotaxy may be used as an alternative to current methods in localizing the IAC in patients with small vestibular schwannomas or intractable vertigo undergoing middle fossa surgery.

Cholesterol granulomas of the petrous apex: combined neurosurgical and otological management.

Cholesterol granulomas of the head are relatively rare. Isolated lesions of the cerebellopontine angle are even more uncommon. In this report, 17 cases of petrous apex cholesterol granulomas are presented and management is discussed. Symptoms at presentation included dizziness (14 patients), pressure (nine patients), tinnitus (eight patients), hearing loss (eight patients), otalgia (six patients), headache (six patients), nausea (three patients), drainage from ear (two patients), facial pain (two patients), seizure (two patients), lightheadedness (one patient), hemifacial spasm (one patient), and facial numbness (one patient). Six cases were managed without surgery and 11 patients underwent operative procedures. The approaches used included the infralabyrinthine (eight patients), transcanal-infracochlear (two patients), and translabyrinthine (one patient). The mean follow-up period for all cases was 29.5 months. Of those patients managed without surgery, symptoms improved in all except one, whose tinnitus was slightly worse. Of surgically treated patients, symptoms improved or remained the same except in one with worsened dizziness. There were nine patients with hearing present presurgery and seven whose hearing was preserved postsurgery. The authors present a case that was managed at another center where an attempt at surgical resection through a subtemporal middle fossa approach was unsuccessful. This lesion was successfully treated using an infralabyrinthine approach with drainage into the mastoid cavity. Cholesterol granulomas of the petrous apex can be managed without surgery when symptoms are stable or improve. Otherwise, a transmastoid extradural approach with simple drainage into the mastoid sinus or middle ear produces symptomatic improvement with low morbidity. Resection of petrous apex cholesterol granulomas is not necessary.

Synthesis and biological evaluation of a series of tyrphostins containing nitrothiophene moieties as possible epidermal growth factor receptor tyrosine kinase inhibitors.

A series of 36 nitrothiophene tyrphostins were synthesized, 32 of which were novel structures. Their ability to inhibit the epidermal growth factor (EGF) receptor tyrosine kinase was assessed in a cell-free assay. Compounds containing a dinitrile, 2-aminoethene-1, 1-dinitrile or a thioamide group were good inhibitors of the receptor tyrosine kinase. Although anti-proliferative and cytotoxic activity was seen, no evidence of inhibition of EGF receptor autophosphorylation in intact cells was observed. The compounds showed no preferential inhibition of EGF-dependent proliferation of fibroblasts transfected with the EGF receptor. Furthermore, in a panel of squamous cell carcinoma cell lines with varying levels of EGF receptor expression, there was no selective cell kill of lines with the highest EGF receptor expression. The 2-nitro-5-substituted-thiophenes and the 2-nitro-3-substituted-thiophenes showed reduction potentials falling within the range likely to be reduced by cellular reducing agents, while the 2-nitro-4-substituted-thiophenes and 4-nitro-2-substituted-thiophenes did not. Compounds from the 2-nitro-5-substituted-thiophene series were shown to induce DNA damage, while no evidence of DNA damage was demonstrated with compounds from the 2-nitro-4-substituted-thiophene series. The 2-nitro-5-substituted-thiophene compound 4 showed significant tumour-type selectivity in the US National Cancer Institute human tumour cell line panel. The leukaemia cell lines were particularly sensitive to the compound, as were the majority of the colon cancer, melanoma and breast cancer cell lines, while the central nervous system-derived lines and the non-small cell lung cancer lines were particularly resistant. Further work is required to determine the precise mechanisms involved in these effects.

Targeted infusions of supradose Cisplatin with systemic neutralization for carcinomas invading the temporal bone.

In an attempt to improve the dismal prognosis for patients with advanced cancer involving the temporal bone, a regional chemotherapy technique was piloted as part of the multimodality therapy for such patients. Rapid supradose cisplatin infusions selectively delivered to the lesion were given to 14 patients with carcinoma involving the temporal bone. Concurrent systemic cisplatin neutralization was achieved with sodium thiosulfate which permitted the use of cisplatin dose intensity regimens equivalent to fivefold the conventional amount. Four patients received chemotherapy alone, four had concomitant irradiation, and six had subsequent irradiation and/or temporal bone surgery. All patients tolerated the chemotherapy without significant complications or toxicity.All three of the patients with previously untreated disease responded to chemotherapy (2 Crs, 1 PR); three of the seven patients with recurrent disease responded to chemotherapy; and all four patients treated with chemoradiation had a complete response (including one patient with recurrent disease). The median follow-up time was 19 months (range, 5 to 63 months). Nine of the 14 patients are alive, including the 4 who were treated with targeted chemoradiation.The use of targeted high-dose chemotherapy for patients with malignant skull base lesions offers hope for improved outcome, particularly when this regimen is given simultaneously with radiation.

Cytological changes preceding cervical cancer.

Cervical smears were reviewed from 62 women who developed squamous carcinoma of the cervix up to 18 years later. The findings indicate that the prevention of cervical cancer by screening depends very largely on the detection of severe dyskaryosis. In this series there was no evidence that mild dyskaryosis was a forerunner of invasive disease. Cytology during the evolution of squamous carcinoma is not characterised by a dyskaryosis which progressively increases in severity. Instead the findings support new concepts that cervical cancer generally arises from an aggressive CIN 3 lesion widely present in the cervix, and in our series, established years before invasion occurs. It would be more useful to report cytology as showing either a low or high grade abnormality rather than distinguishing between different degrees of dyskaryosis.

Negative cytology preceding cervical cancer: causes and prevention.

AIM: To assess the validity of negative cervical smear reports in women who subsequently developed cervical cancer; and to determine means of improving the screening process. METHODS: One hundred and forty cervical smears, initially reported as negative from 103 women, and taken up to 12 years before diagnosis of cervical cancer, were reviewed. RESULTS: Ninety two smears contained dyskaryotic cells. Analysis showed that these smears formed several well defined patterns. False negative reports were likely to occur if fragments of neoplastic tissue rather than dissociated dyskaryotic cells were present or if the smear contained few dyskaryotic cells. Screening fatigue appeared to be a factor in others. It was also considered important that smears contained cells from the endocervix. These were deficient in 64% of the 47 smears confirmed as negative on review and in 69% of smears containing only a few dyskaryotic cells. CONCLUSIONS: Current methods of quality assurance will not remedy these defects in the screening process. It is the responsibility of laboratories to identify sources of poor smears and liaise with smear takers to ensure an improvement in quality. Assessment of the quality of smears received by a laboratory should become an important part of audit. Staff training should place more emphasis on the interpretation of "microbiopsies". The adoption of a quick scanning technique before conventional screening would probably also substantially reduce false negative results.

Myeloma--results of treatment 1986-1990.

Sixty-nine patients with multiple myeloma diagnosed during a five year period at the Belfast City Hospital were followed until death or for a minimum of one year in a retrospective study of survival. Although the patients were unselected, survival data was found to be similar to results from trials in which patient selection had occurred. Overall median survival was thirty-two months. Median survival fell with advancing disease and was 47, 27 and 18 months for Durie-Salmon stages I, II and III respectively. Those patients presenting with a platelet count of < 100 x 10(9)/1 had a median survival of eight months in contrast to those with a platelet count > 100 x 10(9)/1 whose median survival was 36 months. Patients presenting in renal failure had a shorter median survival of 28 months compared to 46 months for those with normal renal function.

The changing pattern of cervical cancer in Northern Ireland 1965-1989.

There was a change in pattern of an increased prevalence of cervical cancer in Northern Ireland from 1965 to 1989, characterised by an increased incidence in women under 40 years. These changes occurred despite special screening of younger women, although the screening programme has probably prevented an even greater increase in incidence of the disease. To reduce the incidence of cervical cancer, not only systematic screening but also cervical smears at more frequent intervals would be required.

The extended maxillotomy and subtotal maxillectomy for excision of skull base tumors.

An approach to tumors of the middle compartment of the skull base is described with three case reports. It is accomplished by extending the subtotal maxillectomy or maxillotomy to include removal of a part of the malar bone, coronoid process of the mandible, nasal turbinates, ethmoid and sphenoid sinuses, posterior nasal septum, and pterygoid plates. Extension of the incision through the anterior tonsillar pillar and lateral pharyngeal wall into the retropharyngeal space will assist to expose the craniocervical region from the sphenoid roof to the fifth cervical vertebra and the skull base between each eustachian tube and carotid canal. The function of the trigeminal, facial, and hypoglossal nerves, hearing, and nasal airway are preserved without mastoidectomy. A temporalis muscle flap closes the defect. Dysphagia and aspiration are not handicaps.

Immunoglobulin light chains in common acute lymphoblastic leukaemia.

A single immunoglobulin light chain lambda was identified in the blast cells of two out of 12 patients with common acute lymphoblastic leukaemia (C-ALL) using the alkaline phosphatase/anti-alkaline phosphatase (APAAP) technique. Inhibition at the cell surface proved that the reaction was a genuine anti-lambda reaction. Immunoglobulin mu chain was not identified in these patients. Results of immunoglobulin typing in 103 patients with B chronic lymphocytic leukaemia (B-CLL) are cited to show the increased sensitivity of the APAAP technique as compared to the indirect immunoperoxidase technique for cellular immunoglobulin identification.