Exploratory thoracotomy on a patient with previous malignancy—“metastasis” or “new primary” or “unrelated lesion”

Surgical resection of a solitary pulmonary metastasis is an established procedure. A medical generation ago when such a shadow appeared on chest roentgenogram of a patient who had known cancer elsewhere in body, it was assumed to be “metastasis” from an extrathoracic site. With increasing advances in knowledge, the occurrence of second primary or new lesion is now no more curiosity in clinical practice. To one's surprise, the lesions that are assumed to be metastatic have often turned out to be “fresh” lesion or even unrelated benign, granulomatous, inflammatory, or parasitic lesion. This paper analyses 66 patients during a period of 20 years who underwent thoracotomy for such solitary pulmonary lesions, and emphasizes the role of diagnostic-cum-therapeutic-thoracotomy in such a clinical situation where in prethoracotomy tissue diagnosis is not forthcoming.     

“Early” tongue carcinoma

This is a retrospective study done in 89 patients who were treated for stage I lingual carcinoma, to determine the local control and 5-year salvage rate and the site and frequency of recurrences with salvage rate with a second modality.     

A phase 2 pilot trial of low‐dose,continuous infusion,or “metronomic” paclitaxel and oral celecoxib in patients with metastatic melanoma

BACKGROUND:

Tumor angiogenesis has been associated with a poor prognosis in patients with metastatic melanoma (MM). Microtubule stabilizers and cyclooxygenase 2 (COX‐2) inhibitors, alone and in combination, have produced inhibitory effects on endothelial cells and tumor angiogenesis. Angiogenesis, which is the growth of new blood vessels, is necessary for tumor growth and progression. Thus, the authors tested the safety and efficacy of a low dose of paclitaxel and celecoxib in patients with MM.

METHODS:

Patients received paclitaxel 10 mg/m² for 96 hours weekly as a continuous intravenous infusion and oral celecoxib 400 mg twice daily. Systemic tumor response was assessed at 6‐week intervals. Tumor measurements at the end of Cycle 1 were used as the baseline for assessment of tumor progression. Patients with unacceptable toxicity or disease progression after Cycle 2 relative to the end of Cycle 1 were taken off study.

RESULTS:

Twenty patients were enrolled. Twelve of 20 patients (60%) had received ≥2 previous systemic therapies. Three patients did not receive treatment because of rapid disease progression. Treatment‐related grade 3/4 toxicities were limited to catheter‐related complications. One patient achieved a partial response, and 3 of 20 patients (15%) had stable disease for >6 months. The median time to progression was 57 days (95% confidence interval, 43‐151 days), and the median overall survival was 212 days (95% confidence interval, 147‐811 days).

CONCLUSIONS:

Low‐dose, continuous intravenous infusion paclitaxel and oral celecoxib produced disease stabilization in a significant proportion of heavily pretreated patients with MM. These findings support a role for metronomic therapy in patients with this disease. Cancer 2010. © 2010 American Cancer Society.     

Resistance to “Castration‐Resistant”

The author challenges the use of the phrase “castration resistance,” which is widely used in the literature and also appears in a recent article by Merseburger et al.In a recent article in The Oncologist, Merseburger et al. [1] outline perspectives arising from current progress in the treatment of advanced prostate cancer (PC). As a nonspecialist in this area, I found their account effectively addresses the challenges posed by this difficult clinical problem. However, I take this opportunity to challenge in turn the widely used phrase “castration resistance.”More than half a century ago, it was established that growth of PC was reduced by bilateral orchiectomy [2], and the rough term “castration” was commonly used. Then it was found that a similar therapeutic effect could be achieved alternatively by the administration of hormone-related agents such as diethylstilbestrol or goserelin [3]: such approaches became known as “chemical castration” (but the adjective was often dropped). Because the growth of PC (just as the development of the normal prostate itself) depends on androgens through androgen-receptor (AR) signaling, there was a sound rationale for these therapeutic procedures of androgen deprivation, frequently called more loosely “hormonal treatments.”Unfortunately, however, all of these beneficial interventions proved time-limited, as PC eventually resumes growth: one might have presumed that it had become independent of AR signaling. However, it transpired that things were not that simple. In an authoritative paper [4] published in 2004, the evidence was reviewed that when PC relapses after hormonal treatment, AR signaling is still on, due to two possible explanations: (a) androgens had not been completely eliminated (they are produced by the adrenal glands and sometimes by the PC itself); (b) even in complete absence of the androgen ligand, AR signaling can still operate through devious means (including AR mutation/amplification, crosstalk-mediated activation of other signaling pathways, and other mechanisms [4, 5]). From then on, the phrase “castration-resistant PC” (CRPC) became popular (n = 1,795 in PubMed).Perhaps the time has come to abrogate this term. First, from the clinical point of view for patients who have CRPC, there are now different remedies available depending on whether the resistance results from (a) or (b) above (e.g., abiraterone versus enzalutamide); thus, the term may cause confusion rather than clarity. Second, we should restore dignity to both patients and terminology. It was a disrespectful mistake in the past to indulge in the phrases “castration” and “chemical castration.” CRPC is worse, and I have even come across the variant “castration-resistant patients,” which some patients perceive as an accusation of refusing to accept something to which unfortunately they have been already subjected. One oncologist told me he used to use the term “castration resistance” freely, but, having PC himself, he has now changed his mind. Instead of CRPC, he suggests, for the two above-mentioned types, respectively, (a) “androgen-deprivation-resistant PC due to persistence of residual androgen” and (b) “androgen-depletion-resistant PC due to androgen-independent persistence of AR signaling.” I admit that these phrases are a bit cumbersome. More simply, androgen deprivation-resistant PC and androgen depletion-resistant PC could both be covered by ADRPC (and they could be called ADPRC-a, ADPRC-b), but the choice of appropriate acronyms is best left to the experts.     

Direct “Metrizamide” Myelocystography in Syringohydromyelia

Metrizamide myelography, followed by CT examination, demonstrated features consistent with syringohydromelia in three patients. One was an adult, male, of 23 years and two were females of 5 and 6 years respectively. Subsequently, metrizamide was introduced into the syrinx by direct needle puncture in each patient. The anatomical details of the syrinx are well demonstrated, continuity of the myelocyst is easily established, and the possibility of communication with the fourth ventricle is readily assessed. The technique is simple and was without complication in these cases. The myelo-graphic and CT findings are also presented. The Arnold-Chiari Type I malformation was present in two patients. The myelocyst did not communicate with the fourth ventricle in two patients. Poor communication was demonstrated in one patient by CT examination immediately after the myelocystogram.     

Exchanging dual‐lumen central venous catheters: How I do it

The management of a blocked long‐term central venous catheter has traditionally been removal and re‐siting, even when device failure is not associated with venous thrombosis or sepsis. It is not possible to ‘railroad’ a split dual‐lumen central venous catheter down a long tortuous s.c. tunnel. Our exchange technique was designed to salvage the tunnel and venous access site in a long‐term catheter that has had uncomplicated primary device failure. In this technique we divide the dual‐lumen catheter and secure the venous access site and the s.c. tunnel with separate peel‐away sheaths. The new catheter is then introduced in the conventional manner through the two peel‐away sheaths, which are then removed. The key advantage of the technique is that it preserves one of the few central venous access sites available. This article describes exchange of an internal jugular catheter, but the same technique is applicable to subclavian catheters.     

Complications of Cerebral Angiography–Catheter Technique

The complications of cerebral angiography in a two-year period where catheter techniques have been preferred to direct puncture have been reviewed. The aetiology of these complications have been discussed, together with methods to reduce such complications to a minimum. It is concluded that, in many cases, the catheter approach is to be preferred, but it requires a meticulous technique if complications are to be avoided. As a result of this review, and in spite of the complications described, we are continuing to use the catheter approach when multiple or selective arteriography is indicated in patients under the age of 60 years and in all infants and children.     

Melanoma metastatic to “lipomata”

Three patients presented with solitary melanoma metastases that mimicked a simple “lipomata.” On further investigation each patient had a discrete fatty tissue tumor mass surrounding a melanoma metastasis. The presence of an enlarging mass in patients with a history of melanoma should be viewed with suspicion and a biopsy should be performed.     

“Hard” and “soft” lesions underlying the HLA class I alterations in cancer cells: Implications for immunotherapy

The ability of cancer cells to escape from the natural or immunotherapy‐induced antitumor immune response is often associated with alterations in the tumor cell surface expression of Major Histocompatibility Complex (MHC) Class I antigens. Considerable knowledge has been gained on the prevalence of various patterns of MHC Class I defects and the underlying molecular mechanisms in different types of cancer. In contrast, few data are available on the changes in MHC Class I expression happening during the course of cancer immunotherapy. We have recently proposed that the progression or regression of a tumor lesion in cancer patients undergoing immunotherapy could be predetermined by the molecular mechanism responsible for the MHC Class I alteration and not by the type of immunotherapy used, i.e., interleukin‐2 (IL‐2), Bacillus Calmette‐Guèrin (BCG), interferon‐alpha (IFN‐α), peptides alone, dendritic cells loaded with peptides, protein‐bound polysaccharide etc. If the molecular alteration responsible for the changes in MHC Class I expression is reversible by cytokines (“soft” lesion), the MHC Class I expression will be upregulated, the specific T cell–mediated response will increase and the lesion will regress. However, if the molecular defect is structural (“hard” lesion), the MHC Class I expression will remain low, the escape mechanism will prevail and the primary tumor or the metastatic lesion will progress. According to this idea, the nature of the preexisting MHC Class I lesion in the cancer cell has a crucial impact determining the final outcome of cancer immunotherapy. In this article, we discuss the importance of these two types of molecular mechanisms of MHC Class I–altered expression.     

Colorectal cancer—prognostic signs in “local disease”

This detailed review of the clinical and pathologic signs which effect the prognosis of patients with colorectal cancer. The following are reviewed: (1) the degree of cellular anaplasia, (2) local penetration of the bowel wall, (3) lymph-node spread, (4) venous invasion, (5) perineural invasion, (6) obstruction and perforation, and (7) the number of cm the lesion is located from the anal verge.     

So‐called “malignant blue nevus”

BACKGROUND:

Melanomas that arise in association with or that resemble blue nevi are extremely rare and have been termed “malignant blue nevi.” The authors report on a single‐institutional clinicopathologic study of “blue nevus‐like melanomas” (BNLMs).

METHODS:

Twenty‐six patients were identified with a “malignant blue nevus” over 29 years at the Sydney Melanoma Unit. Twenty‐three patients were included in the current study after pathologic review. Clinical outcomes of those patients were compared with the outcomes in a matched control group of patients with melanoma (matched for age, sex, Breslow thickness, Clark level, ulceration, and anatomic site).

RESULTS:

The median patient age was 44 years, and men comprised 65% of the patients. The tumors were distributed evenly among skin sites, and their median Breslow thickness was 5.5 mm. After a median follow‐up of 36.5 months, there was no difference in survival (P = .702) between patients with BNLM and patients in the control group.

CONCLUSIONS:

BNLMs tended to present at a more advanced stage, with thicker primary tumors, but had a metastatic pattern comparable to and was not more aggressive in behavior than other types of melanoma. The authors concluded that BNLMs should be treated in the same way as any other melanoma variants based on clinical staging and pathologic prognostic indices. Cancer 2009. © 2009 American Cancer Society.     

Near‐infrared photoimmunotherapy (NIR‐PIT) on cholangiocarcinoma using a novel catheter device with light emitting diodes

Near‐infrared photoimmunotherapy (NIR‐PIT) is a novel therapy for cancers that uses NIR light and antibody‐photosensitizer (IR700) conjugates. However, it is difficult to deliver NIR light into the bile duct for cholangiocarcinoma (CCA) from the conventional extracorporeal apparatus. Thus, in this study, we developed a dedicated catheter with light emitting diodes (LEDs) that supersedes conventional external irradiation devices; we investigated the therapeutic effect of NIR‐PIT for CCA using the novel catheter. The new catheter was designed to be placed in the bile duct and a temperature sensor was attached to the tip of the catheter to avoid thermal burn. An anti‐epidermal growth factor receptor (EGFR) antibody, Panitumumab‐IR700 conjugate or anti‐human epidermal growth factor receptor type 2 (HER2) antibody, Trastuzumab‐IR700 conjugate, was used with EGFR‐ or HER2‐expressing cell lines, respectively. The in vitro efficacy of NIR‐PIT was confirmed in cultured cells; the capability of the new catheter for NIR‐PIT was then tested in a mouse tumor model. NIR‐PIT via the developed catheter treated CCA xenografts in mice. NIR‐PIT had an effect in Panitumumab‐IR700 conjugate‐ and Trastuzumab‐IR700 conjugate‐treated CCA cells that depended on the receptor expression level. Tumor growth was significantly suppressed in mice treated with NIR‐PIT using the novel catheter compared with controls (P < .01). NIR‐PIT was an effective treatment for EGFR‐ and HER2‐expressing CCA cells, and the novel catheter with mounted LEDs was useful for NIR‐PIT of CCA.     

NISBET SYMPOSIUM “Current Medical Politics and Peer Review”

Australia's resources are finite and limited. Cash outlays by the government for health care have risen at a rate which cannot continue indefinitely as an increasing share of the national purse. It follows that as a profession, medical practitioners cannot do everything scientifically possible for everyone everywhere. New advances are seen to require new skills and techniques as much as new high cost gadgets. Radiology is a particularly costly sub-speciality which is almost uniquely capital intensive. The present danger is that radiologists are coming to be viewed as professionals engaged in a conspicuous consumption of scarce national resources while morbidity and mortality figures are not showing an improvement remotely proportionate to the increased expenditure. Examples of over use of resources together with private investment in high cost technology are outlined, and issues of accountability and of the need for clearly stated goals are discussed. A role for the Royal Australasian College of Radiologists in monitoring the efficiency, diagnostic yield and the general effectiveness of radiological examinations is considered. If organised medicine is found unequal to the task of rationalising the use of resources, then this role may come to be assumed by others.     

The “Distorted Spoke” Sign of Malignant Gastric Ulceration

A new term, “the distorted spoke sign”, is used to describe the mucosal folds of malignant gastric ulceration. The ends of the gastric folds near the edge of a malignant gastric ulcer may show one or more of the following appearances: sudden cut-off, sudden tapering, swelling, erosion of one edge, or erosion of both edges.     

Does “Black” Brain Mean Doom? Computed Tomography in the Prediction of Outcome in Children with Severe Head Injuries: “Benign” vs “Malignant” Brain Swelling

A retrospective review of initial and subsequent CT scans of 179 children who has suffered severe head injury requiring admission to intensive care was performed. The aim was to define the CT appearance which was always associated with a poor outcome. The children whose brain showed poor definition of basal ganglia and grey-white differentiation overall, together with sufficient swelling to obliterate the ambient cistern and third ventricle always died or remained in a vegetative state. Over half of these had reduced brain density, and several had small focal high densities consistent with contusions or petechial haemorrhages. A typical appearance showed homogeneous scans at the levels of the ambient cistern and thalami with no normal internal brain detail. Conversely obliteration of the ambient cistern associated with a large surface collection was compatible with complete recovery if grey-white definition remained normal and treatment was prompt.     

“FISHing” to detect urinary and other cancers

BACKGROUND:

The UroVysion Bladder Cancer Kit detects amplifications of chromosomes 3, 7, and 17, and the deletion of 9p21, by fluorescence in situ hybridization (FISH). Because manual interpretation of UroVysion FISH is time consuming and can be challenged by variable probe signal strengths and background labeling, the authors investigated an automated image analysis system to improve throughput, productivity, quality control, and accuracy.

METHODS:

The authors evaluated the interactive BioView Duet imaging system as an aid to UroVysion FISH interpretation in a 2‐armed, blinded comparison with manual screens of the same 135 consecutive cases. Manual and Duet‐assisted interpretations were compared with respect to concordance, reproducibility, and timing.

RESULTS:

Eighty‐one cases were interpreted as positive or negative with 94% concordance and a kappa value of 0.84 between manual and Duet‐aided interpretations. Three cases that ultimately were judged positive were detected with the aid of Duet but were missed with a manual screen. A final interpretation could not be given for≈25% of Duet‐scanned cases. Duet‐aided interpretation was highly reproducible for patient and control slides. Pathologist evaluation time per case was 4 minutes compared with 30 minutes for manual interpretation. Cytotechnologist involvement added 18 minutes for a total of 22 minutes, a savings of 8 minutes per case.

CONCLUSIONS:

Duet‐aided interpretations were at least equivalent to manual interpretations. The system permitted interactive review of abnormal cells and had the ability to evaluate the same cells for brightfield cytology followed by FISH. The image processing and analysis tools of the Duet system enhanced the morphology skills of cytology professionals in providing accurate interpretations. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.