Clinical implications of acellular mucin pools in resected rectal cancer with pathological complete response to neoadjuvant chemoradiation.

AIM: Approximately 20% of rectal cancers treated with neoadjuvant chemoradiation achieve a pathological complete response (pCR), which is associated with an improved oncological outcome. However, in a proportion of patients with a pCR, acellular pools of mucin are present in the surgical specimen. The aim of this study was to evaluate the clinical implications of acellular mucin pools in patients with rectal adenocarcinoma achieving a pCR after neoadjuvant chemoradiation followed by proctectomy. METHOD: A single-centre colorectal cancer database was searched for patients with clinical Stage II and Stage III rectal adenocarcinoma who achieved a pCR (i.e. ypT0N0M0) after neoadjuvant chemoradiation followed by proctectomy between 1997 and 2007. Patients were categorized according to the presence or absence of acellular mucin pools in the resected specimen, and groups were compared. Patient demographics, tumour and treatment characteristics, and oncological outcomes were recorded. Primary outcomes were 3-year local and distant recurrences, and disease-free and overall survivals. RESULTS: Two hundred and fifty-eight patients with clinical Stage II or Stage III rectal adenocarcinoma were treated by neoadjuvant chemoradiation. Fifty-eight of these patients had a 58 pCR. Eleven of the 58 patients with a pCR had acellular mucin pools in the surgical specimen. The median follow up was 40 months. The groups were statistically similar with respect to demographics, chemoradiation regimens, distance of tumour from the anal verge, clinical stage and surgical procedure. No patient had local recurrence. Patients with acellular mucin pools had increased distant recurrence (21%vs 5%), decreased disease-free survival (79%vs 95%) and decreased overall survival (83%vs 95%) rates, although none of these differences was statistically significant. CONCLUSION: The presence of acellular mucin pools in a proctectomy specimen with a pCR does not affect local recurrence, but may suggest a more aggressive tumour biology.

Genetic and epigenetic classifications define clinical phenotypes and determine patient outcomes in colorectal cancer.

BACKGROUND: A molecular classification of colorectal cancer has been proposed based on microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and mutations in the KRAS and BRAF oncogenes. This study examined the prevalence of these molecular classes, and differences in clinical presentation and outcome. METHODS: Demographics, tumour characteristics and survival were recorded for 391 subjects with colorectal cancer. Tumour DNA was analysed for MSI (high (MSI-H) or microsatellite stable (MSS)), CIMP (high (CIMP-H) or no (CIMP-neg)) and BRAF and KRAS mutations. Clinical differences between four phenotypes were examined. RESULTS: Most tumours were MSS/CIMP-neg (69.8 per cent), with a nearly equal distribution of MSI-H/CIMP-H, MSI-H/CIMP-neg and MSS/CIMP-H types. MSS/CIMP-neg tumours were less likely to be poorly differentiated (P = 0.009). CIMP-H tumours were more common in older patients (P < 0.001). MSI-H/CIMP-H tumours had a high frequency of BRAF mutation and a low rate of KRAS mutation; the opposite was true for MSS/CIMP-neg tumours (P < 0.001). The four molecular phenotypes tended towards divergent survival (P = 0.067 for stages 1-III). MSI-H cancers were associated with better disease-free survival (hazard ratio 2.00 (95 per cent confidence interval 1.03 to 3.91); P = 0.040). CONCLUSION: Colorectal cancers are molecularly and clinically heterogeneous. These different molecular phenotypes may reflect variable prognosis.

Aneusomy of chromosomes 7, 8, and 17 and amplification of HER-2/neu and epidermal growth factor receptor in Gleason score 7 prostate carcinoma: a differential fluorescent in situ hybridization study of Gleason pattern 3 and 4 using tissue microarray.

Recent evidence shows that the proportion of poorly differentiated prostate carcinoma (Gleason pattern [GP] 4/5) is a surrogate factor for biochemical failure after radical prostatectomy (RP). However, little is known about specific molecular and cytogenetic changes in this aggressive component of localized prostate cancer. We constructed a tissue microarray containing areas of GP 3 and 4 from formalin-fixed radical prostatectomy specimens of 39 patients with Gleason score 7 carcinoma (>or=50% GP 4), known pathologic staging parameters (stage < T3b), and biochemical failure data (mean follow-up, 30 months; range, 5 to 74 months). Interphase fluorescent in situ hybridization (FISH) was performed on 5-microm microarray sections using pericentromeric probes to chromosomes 7, 8, and 17 and probes for the HER-2/neu and epidermal growth factor receptor (EGFR) genes. Low-level amplification of HER-2/neu was found in 26% of cases (3 to 5 signals per nucleus, corrected for chromosome 17 aneusomy). Aneusomy of chromosomes 7, 8, and 17 was identified in 21%, 15%, and 5% of cases, respectively. All aberrations occurred almost exclusively in GP 4 carcinoma (8 of 8 aneusomies 7, 2 of 2 trisomies 17, 9 of 10 HER-2/neu amplifications, and 5 of 6 aneusomies 8; P < .001). The presence of HER-2/neu amplification was associated with high tumor volume (>2.0 cm(3), P = 0.004). Among patients with negative surgical margins, gain of chromosome 7 was associated with biochemical failure after RP (P =.004, log-rank). Amplification of the EGFR gene occurred in only 1 case (3%). Significant differences in HER-2/neu amplification and gain of chromosomes 7, 8, and 17 were detected between GP 4 prostate carcinoma and GP 3. The frequency of aberrations increased with tumor volume. Chromosome 7 abnormalities may play an important role in cancer progression in margin-negative patients. EGFR amplification was rare, suggesting that this oncogene is not altered at the gene copy number level.

Effects of cardiac oscillations and lung volume on acinar gas mixing during apnea.

We evaluated the importance of cardiogenic gas mixing in the acini of 13 dogs during 2 min of apnea. 133Xe (1-2 mCi in 4 ml of saline) was injected into an alveolar region through an occluded pulmonary artery branch, and washout was measured by gamma scintillation scanning during continued occlusion or with blood flow reinstated. The monoexponential rate constant for Xe washout (XeW) was -0.4 +/- 0.08 (SE) min-1 at functional residual capacity (FRC) with no blood flow in the injected region. It decreased by more than half at lung volumes 500 ml above and 392 ml below FRC. With intact pulmonary blood flow, XeW was -1.0 +/- 0.08 (SE) min-1 at FRC, and it increased with decreasing lung volume. However, if calculated Xe uptake by the blood was subtracted from the XeW measured with blood flow intact, resulting values at FRC and at FRC + 500 ml were not different from XeW with no blood flow. Reasonable calculation of Xe blood uptake at 392 ml below FRC was not possible because airway closure, increased shunt, and other factors affect XeW. After death, no significant XeW could be measured, which suggests that XeW caused by molecular diffusion was small. We conclude that 1) the effect of heart motion on the lung parenchyma increases acinar gas mixing during apnea, 2) this effect diminishes above or below FRC, and 3) there is probably no direct effect of pulmonary vascular pulsatility on acinar gas mixing.

Regional chest wall impedance during nonrespiratory maneuvers.

To assess changes in total and regional chest wall properties during nonrespiratory maneuvers, we measured electromyographic activity of various chest wall muscles, esophageal pressure, and rib cage and abdominal surface displacements in six subjects before and during various static tasks. Subjects were seated at functional residual capacity, and quasi-sinusoidal forcing at the mouth (0.4 Hz, 500 ml) was imposed during the maneuver in the absence of active breathing. Magnitude of total chest wall impedance (magnitude of Zw) increased with effort during all maneuvers; changes in phase were small. Maneuvers involving primarily muscles of the neck and rib cage--holding a 10-kg weight, 10 kg of isometric tension between the arms, and isometric neck flexion--roughly doubled the magnitude of rib cage impedance (magnitude of Zrc) and, to a lesser degree, increased magnitude of diaphragm-abdomen impedance (magnitude of Zd-a). Unilateral and bilateral leg lifts, in addition to increasing magnitude of Zd-a, increased magnitude of Zrc. Passive 90 degrees rotation of the torso caused approximately 25% increases in magnitude of Zrc and magnitude of Zd-a; if the rotation was actively maintained by the trunk muscles, both regional impedances increased over 100%. Increases in magnitude of regional impedance were correlated to increases in regional electromyographic activity; changes in phase were small. Passive restriction of rib cage displacement by strapping increased magnitude of Zrc and magnitude of Zw but not magnitude of Zd-a, whereas abdominal strapping increased magnitude of Zd-a but did not affect magnitude of Zrc or magnitude of Zw.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunohistochemistry in the differential diagnosis of acinar and endocrine pancreatic neoplasms.

Histologic differential diagnosis of acinar cell carcinoma (ACC), mixed acinar-endocrine cell carcinoma (MAEC), and pancreatic endocrine tumors (PET) can be difficult but is important because of differences in their clinical behavior. This study investigates the utility of immunohistochemistry (IHC) in this differential diagnosis using immunohistochemical stains that are available in most laboratories. IHC was performed on paraffin-embedded tissue in ACC (n = 6), MAEC (n = 2), and PET (n = 13), using synaptophysin (SYN), chromogranin (CHR), chymotrypsin (CHY), and alpha-1-antitrypsin (AAT). Electron microscopy (EM) was performed in all cases to confirm the diagnosis. Long-term follow-up and death of disease (DOD) was known in all patients. The ACCs stained as follows: CHY (4/6), AAT (3/6), SYN (4/6); CHR was negative in all cases. Both cases of MAEC stained with CHY, AAT, and SYN (2/2); CHR was negative. PET stained as follows: SYN (13/13), CHR (8/13), CHY (4/13), AAT (5/13). In the ACC/ MAEC group, six of eight patients were DOD at mean follow-up of 11 months. Among the PET, two of 16 patients were DOD at mean follow-up of 37 months. Considerable immunophenotypic overlap exists between ACC, MAEC, and PET. Consequently, one can neither confirm nor rule out a diagnosis of ACC or MAEC using generally available immunohistochemical stains alone. These findings support a role for EM in the evaluation of exocrine and endocrine pancreatic neoplasms.

Laparoscopic renal autotransplantation.

BACKGROUND AND PURPOSE: Renal autotransplantation is an extensive open surgical operation consisting of two distinct procedures, live-donor nephrectomy and autotransplantation, and requiring two large skin incisions. Herein, we analyze the feasibility of performing the entire procedure laparoscopically. MATERIALS AND METHODS: Renal autotransplantation was performed entirely laparoscopically in six female farm pigs. Following a left donor nephrectomy, intracorporeal renal hypothermia was achieved by intra-arterial perfusion of ice-cold solution through a 4F balloon catheter. During autotransplantation, the renal vessels were anastomosed intracorporeally to the previously prepared ipsilateral common iliac vessels in an end-to-side fashion. Laparoscopic freehand suturing (5-0 Prolene) and knot-tying techniques were employed exclusively. A staged contralateral native nephrectomy was performed in five animals. Postoperative follow-up included serial creatinine measurements, intravenous urography, aortography, and renal histologic examination. RESULTS: The mean operating time was 6.2 hours (range 5.3-7.9 hours), the venous anastomosis time was 33 minutes (range 22-46 minutes), the arterial anastomosis time was 31 minutes (range 27-35 minutes), and the total iliac clamping time was 77 minutes (range 62-88 minutes). The total renal ischemia time was 68.7 minutes: warm ischemia 5.1 minutes, cold ischemia 33 minutes and rewarming 31 minutes. Serum creatinine concentrations remained stable: baseline 1.3 mg/dL, after autotransplantation 1.1 mg/dL, and after contralateral nephrectomy 1.6 mg/dL. Intravenous urography and aortography prior to euthanasia (N = 5) demonstrated prompt contrast uptake and excretion by the autotransplanted kidneys and patent arterial anastomoses, respectively. Histopathologic examination of the autograft demonstrated normal renal architecture. CONCLUSIONS: Renal autotransplantation can be performed utilizing laparoscopic techniques exclusively. This study may form the basis for performance of complex urologic vascular procedures laparoscopically.

Laparoscopic orthotopic ileal neobladder.

BACKGROUND AND PURPOSE: Orthotopic ileal neobladder is currently the preferred continent urinary diversion in suitable patients undergoing radical cystectomy for muscle-invasive bladder cancer. To our knowledge, presented herein is the initial report of laparoscopic orthotopic ileal neobladder following cystectomy that was performed completely intracorporeally in a porcine model. MATERIALS AND METHODS: The laparoscopic technique was developed in seven pigs. Subsequently, a long-term survival study was performed in 12 consecutive animals. Laparoscopic cystectomy was performed, preserving the urethral sphincter. An ileal segment of 35 cm (first three animals), 45 cm (next four), or 55 cm (final five animals) with adequate mesentery was isolated; and ileal continuity was restored intracorporeally by a stapled anastomosis. Ileal detubularization for construction of an ileal neobladder, urethroileal anastomosis, and bilateral stented ileoureteral anastomoses to a tubular Studer limb extension were all created completely intracorporeally using only laparoscopic free-hand suturing and knot-tying. Biochemical data (preoperative and serial postoperative hemoglobin, renal panel, blood gases), radiologic studies (intravenous urogram, retrograde pouchgram), functional measures (neobladder urodynamics, Whitaker pressure-flow study of both ureters), and microscopic evaluation of the neobladder and ureteroileal and urethroileal anastomotic sites were obtained to evaluate the long-term functional and anatomic outcome. RESULTS: Completely intracorporeal laparoscopic construction of an ileal orthotopic neobladder was successful in all 12 animals without intraoperative or early postoperative complications or open conversion. The mean operating time was 5.4 hours (range 4.5-6.5 hours), and the blood loss was minimal. All study pigs survived their predetermined follow-up period, ranging from 1 to 3 months. Late complications occurred in three animals: one port-site abscess and two cases of E. coli pyelonephritis and azotemia, leading to one death at 2 months. The mean serum creatinine concentrations were 1.33 mg/dL, 1.61 mg/dL, and 1.55 mg/dL at 1, 2, and 3 months, respectively. The mean neobladder capacity was 420 mL (range 250-700 mL) with pressures < or = 20 cm H2O (range 17-20 cm H2O). Pre-euthanasia Whitaker testing confirmed excellent drainage in all 24 ureters. No ileoureteral or ileourethral anastomotic strictures or leaks were noted on intravenous urography, retrograde pouchgram, or postmortem physical calibration of the anastomotic sites. Histologic examination confirmed excellent healing without obvious fibrosis. CONCLUSION: Laparoscopic construction of an orthotopic neobladder is feasible. The anatomic and functional outcome is excellent and comparable to that of open surgery. Clinical application is imminent.

A case report of intraspinal paracoccidioidomycosis.

The authors report a case of paraplegia caused by a lumbar intraspinal paracoccidioidomycosis (PCM) granuloma. Clinical neurological diagnosis of a compressive spinal cord lesion was confirmed by spinal magnetic resonance imaging (MRI). Patient was submitted to surgery with total excision of the lesion. Histopathological analysis confirmed the diagnosis of PCM. Patient is on sulfamethoxazole/trimethoprim combined with fluconazole and is experiencing positive neurological recovery.

[Susacs syndrome: case report]. / Síndrome de Susac: relato de caso.

We present the case of a 34-year-old woman with clinical picture suggestive of Susacs syndrome, or retinocochlear vasculopathy. This syndrome, which was described for the first time in 1979, is characterized by a clinical triad of encephalopathy, neurosensorial deafness and visual deficit. Its pathogenesis and treatment are still disputed. We have called special attention to differential diagnosis, since this entity has not yet been described in Brazil, and is probably underdiagnosed.

[Iatrogeny. The importance of clinical diagnosis. Myopathies induced by clofibrate]. / Iatrogenia. A importância do diagnóstico clínico. Miopatia induzida por clofibrate.

The authors describe the neurological manifestations of a female patient with hypercholesterolemia who developed myopathy in the course of her treatment with clofibrate. After the drug was tapered off, the neurological signs and symptoms disappeared. Therefore, attention is called for the importance of the differential diagnosis of iatrogenic myopathies with polymyositis.

[Motor neuron disease: metabolic evaluation]. / Doença do neurônio motor. Avaliação metabólica.

The authors studied serum and urinary calcium and phosphorus levels, as well as abnormalities on the spine of 30 patients with motor neuron disease. The authors believe in multifactorial aspects in the pathogenesis of motor neuron disease, calling special attention to toxic and metabolic factors.

[Reduction in glucose concentration in the brain of mice inoculated with cerebrospinal fluid from patients with amyotrophic lateral sclerosis]. / Redução na concentração de glicose no cérebro de camundongos inoculados com líquido cefalorraquiano de pacientes com esclerose lateral amiotrófica.

Using chromatographic analysis the authors studied glucose concentration in the brain of Swiss mice inoculated with CSF of four patients with amyotrophic lateral sclerosis. They found reduction in the levels of glucose, suggesting the existence of an exogenous factor transferred by CSF.

The diagnosis of leprosy among patients with symptoms of peripheral neuropathy without cutaneous lesions: a follow-up study.

Forty-four patients with neuritic leprosy were individually followed for periods ranging from 4 months to almost 4 years for the purpose of ascertaining the presence and/ or absence of leprosy. The neural symptoms presented were sensory impairment (41), parasthesia (28), nerve enlargement (22), nerve tenderness (20), paresia (20), amyotrophy (8). Leprosy was diagnosed in ten out of the total number of patients studied. Leprosy was confirmed by the appearance of reactional neuritis (4), reversal reaction (2), biopsy of the hypoesthesic area (3) and the appearance of non-reactional cutaneous lesion. We reported an experience in the diagnosis of neuritic leprosy and its most frequent clinical presentation with which clinicians have to be acquainted. We can also state that the clinical follow-up was an effective strategy for the diagnosis of the disease when diagnostic facilities are not available or have not confirmed the diagnosis.

[Sporadic amyotrophic lateral sclerosis. Diagnostic criteria]. / Esclerose lateral amiotrófica esporádica. Critérios diagnósticos.

The authors report two cases of amyotrophic lateral sclerosis (ALS) misdiagnosis (a craniocervical junction disorder, and a cervical spinal cord ependymoma). They review some causes of ALS-like syndrome and propose a protocol to be adopted for the study of all patients who present clinical abnormalities suggesting ALS.

Morbidity after day case laparoscopy. A comparison of two techniques of tracheal anaesthesia.

A comparison was made of postoperative morbidity following two anaesthetic techniques for day case laparoscopies. One group of patients was allowed to breathe spontaneously after intubation under suxamethonium. The second group received atracurium and their lungs were mechanically ventilated. Patients in the controlled ventilation group experienced significantly less severe sore throats and muscle pain in the first 24 hours postoperatively than the patients who breathed spontaneously. Both techniques proved to be safe and are suitable for day case laparoscopy. The safety of patients is discussed in relation to the choice of anaesthetic technique used.

Extracorporeal circuit sequestration of fentanyl and alfentanil.

Fentanyl or alfentanil, in doses approximating to those used in clinical practice, was added to the priming fluid of an extracorporeal circuit before the institution of cardiopulmonary bypass (CPB). The concentrations of both drugs in the priming fluid were measured over a 20-min period. The concentration of fentanyl decreased at neutral or high pH values, suggesting drug adsorption to the circuit. The concentration of alfentanil was unaffected. The administration of fentanyl to the priming fluid may produce lower anaesthetic concentrations than anticipated.