Detrimental Immunologic Effects of Preoperative Chemoradiotherapy in Advanced Rectal Cancer

PURPOSE: Preoperative chemoradiotherapy for advanced rectal cancer has been an important therapeutic tool to improve the long-term results of curative resection. It is not known whether preoperative chemoradiotherapy for advanced rectal cancer influences the perioperative course of immune parameters. METHODS: Thirty patients with rectal cancer underwent surgery with (study group, n = 15) or without (control group, n = 15) preoperative chemoradiotherapy (2 cycles of 5-fluorouracil, 45 Gy). Blood samples were taken before neoadjuvant therapy, preoperatively, and on Days 1, 2, and 5 after surgery. Cell numbers of lymphocyte subpopulations, granulocytes, monocytes, and natural killer cells were determined by flow cytometry; tumor necrosis factor- and interleukin-6 serum levels were measured with enzyme-linked immunosorbent assay. RESULTS: Significant differences between study and control patients (P < 0.05) were detected regarding circulating interleukin-6 and tumor necrosis factor- levels, with depression of the proinflammatory response to surgery in study patients. Similarly, granulocytosis and monocytosis after surgery were significantly lower in patients after neoadjuvant therapy. Furthermore, cell counts of total T lymphocytes, T helper cells, B lymphocytes, and natural killer cells were significantly reduced after preoperative chemoradiotherapy. This depression of cell-mediated immunity in study patients was even more pronounced after surgery. CONCLUSIONS: Preoperative chemoradiotherapy for advanced rectal cancer results in a significant preoperative and postoperative immune dysfunction as indicated by depression of lymphocyte subpopulations, monocytes, granulocytes, and proinflammatory cytokine release. These findings are of importance because increased perioperative morbidity and mortality rates have been observed after preoperative chemoradiotherapy.     

Effect of tumour and chemoradiotherapy on oesophageal motility

Background The contribution of dysmotility to dysphagia in oesophageal cancer is unclear. Aim To examine oesophageal motility in patients with oesophageal carcinoma and to assess the effect of chemoradiotherapy on motility. Methods Stationary manometry and 24-hour pH-metry were performed in 12 patients with oesophageal carcinoma and one week following completion of chemoradiotherapy using 5-fluorouracil (5-FU), cisplatin and 40Gy radiotherapy. Results All patients had abnormal motility prior to treatment. Peristalsis was impaired in 11 patients with a mean (SD) of 25% (9) of waves normally propagated. Eight patients had 20% or more simultaneous waves. Following chemoradiotherapy, the percentage of waves normally propagated increased from 25% (9) to 52% (10) (p < 0.03) and normal peristalsis was restored in four patients. The percentage of simultaneous waves decreased from 38% (11) to 21.6% (10) (p=0.129) while the percentage of dropped or increased waves decreased from 20% (11) to 8.3% (4) (p=0.264). Conclusions Oesophageal motility is disturbed in oesophageal cancer. Dysphagia in oesophageal cancer may be partly explained by oesophageal dysmotility. This is improved by chemotherapy.     

Magnetic resonance imaging of penile metastases: A report on five cases

Five cases of penile metastases are presented. Axial and sagittal T1-weighted and T2-weighted scans were performed in all patients. In some, coronal images were also obtained. The penile metastases were most often seen as discrete masses in the corpora cavernosa or corpus spongiosum. An atypical pattern of diffuse infiltration is also illustrated. Limitations of cavernosography, ultrasound (US) and computed tomography (CT) are discussed. The magnetic resonance (MR) features of penile metastases and possible role MR may have in the management of these patients are described.     

Plasmodium vivax: a cause of malnutrition in young children

We studied the aetiology of malnutrition in a cohort of 1511 children < 10 years old in Espiritu Santo, Vanuatu. Malnutrition was categorized using standard anthropometric criteria as: underweight [weight-for-age (WA) Z score < -2], wasting [weight-for-height (WH) Z < -2], or stunting [height-for-age (HA) Z < -2]. On multiple logistic regression analysis, the only factors significantly associated with wasting were age < 5 years [OR (95% CI) 1.8 (1.2-2.9), p = 0.01] and having suffered one or more episodes of clinical P. vivax malaria in the 6 months preceding nutritional assessment [OR 2.4 (1.3-4.4), p = 0.006]. The incidence of P. vivax infection was significantly higher during the 6 months preceding assessment in underweight vs. non-underweight children [incidence rate ratio (IRR) 2.6 (1.5-4.4), p < or = 0.0001). These groups had similar incidences of clinical P. falciparum infection during the same period [IRR 1.1 (0.57-2.1) p = 0.8] and of either species during the 6 months following assessment [IRR P. vivax 1.3 (0.9- 2.0) p = 0.2; IRR P. falciparum 1.3 (0.9-1.9) p = 0.2]. In these children, P. vivax malaria was a major predictor of acute malnutrition; P. falciparum was not. Wasting neither predisposed to nor protected against malaria of either species. Although P. vivax malaria is generally regarded as benign, it may produce considerable global mortality through malnutrition.      

The patient-physician relationship and medical utilization

Objective: The goal of this study was to (1) explore the relationship between medical utilization and characteristics of the patient-physician relationship and (2) evaluate the relationship between physician perception of patient difficulty, chronic medical problems, and patient somatizing tendencies.Method: Patients in an academic family practice center were asked to complete a demographic data sheet, the PRIME-MD Patient Questionnaire, and the Barrett-Lennard Relationship Inventory regarding their relationship with their physicians. Their physicians completed the Difficult Doctor-Patient Relationship Questionnaire. Patient charts were examined for number of office visits and phone calls in the previous year, as well as number of chronic problems and medications. The study was conducted from September 2000 to November 2001.Results: Forms were completed by 165 patients and 20 physicians. Forty-three patients who were approached refused to participate. Patient ratings on the Barrett-Lennard Relationship Inventory were not related to utilization measures. Physician ratings of difficulty were significantly related to phone calls and visits (p < .05), as well as PRIME-MD Patient Questionnaire somatization tendencies (p < .05) but not to number of chronic problems. Patient and physician ratings were not significantly correlated. Gender (p < .001), marital status (p < .04), education (p < .03), and employment status (p < .002) were all related to utilization measures.Conclusion: Medical utilization was associated with somatizing tendencies of patients and the physicians' perception of patient difficulty. Physicians rated patients as difficult if they tended to somatize but not if they had a number of chronic problems.     

Multiple granular cell tumors are an associated feature of LEOPARD syndrome caused by mutation in PTPN11

We report a patient with a clinical and molecular diagnosis of LEOPARD syndrome (LS) associated with multiple granular cell tumors (MGCT). Bidirectional sequencing of exons 7, 12, and 13 of the PTPN11 gene revealed the T468M missense mutation in exon 12. This mutation has been previously reported in patients with LS. To our knowledge, this is the first report of MGCT associated with molecularly characterized LS and provides the first molecular evidence linking granular cell tumors (GCT) to the Ras/mitogen-activated protein (MAP) kinase pathway. We propose that MGCT can be associated with LS. Analysis of GCT from this case tested negatively for loss of heterozygosity (LOH) at the PTPN11 and NF1 loci and did not show deletions of the PTEN gene. The absence of LOH of PTPN11 supports published functional data that T468M is a dominant-negative mutation.     

Bench-to-bedside review: Latest results in hemorrhagic shock

Hemorrhagic shock is a leading cause of death in trauma patients worldwide. Bleeding control, maintenance of tissue oxygenation with fluid resuscitation, coagulation support, and maintenance of normothermia remain mainstays of therapy for patients with hemorrhagic shock. Although now widely practised as standard in the USA and Europe, shock resuscitation strategies involving blood replacement and fluid volume loading to regain tissue perfusion and oxygenation vary between trauma centers; the primary cause of this is the scarcity of published evidence and lack of randomized controlled clinical trials. Despite enormous efforts to improve outcomes after severe hemorrhage, novel strategies based on experimental data have not resulted in profound changes in treatment philosophy. Recent clinical and experimental studies indicated the important influences of sex and genetics on pathophysiological mechanisms after hemorrhage. Those findings might provide one explanation why several promising experimental approaches have failed in the clinical arena. In this respect, more clinically relevant animal models should be used to investigate pathophysiology and novel treatment approaches. This review points out new therapeutic strategies, namely immunomodulation, cardiovascular maintenance, small volume resuscitation, and so on, that have been introduced in clinics or are in the process of being transferred from bench to bedside. Control of hemorrhage in the earliest phases of care, recognition and monitoring of individual risk factors, and therapeutic modulation of the inflammatory immune response will probably constitute the next generation of therapy in hemorrhagic shock. Further randomized controlled multicenter clinical trials are needed that utilize standardized criteria for enrolling patients, but existing ethical requirements must be maintained.     

Ileus bei ausgedehnten intraabdominellen Verkalkungen nach Peritonitis

Zusammenfassung. Wir berichten über einen 48 j?hrigen Patienten. In Folge einer bakteriellen Peritonitis hatten sich ausgedehnte intraabdominelle Verkalkungen gebildet. Diese hatten einen Obstruktionsileus verursacht. Im Rahmen einer Revisionslaparotomie wurden die Kalkspangen entfernt. Zur Rezidivprophylaxe veranla?ten wir eine percutane Bestrahlung mit 15 Gy. Zus?tzlich erfolgte eine systemische Indometacin-Applikation. Eine Literaturrecherche ergab nur 2 vergleichbare F?lle.      

Novel orthobunyavirus in Cattle, Europe, 2011

In 2011, an unidentified disease in cattle was reported in Germany and the Netherlands. Clinical signs included fever, decreased milk production, and diarrhea. Metagenomic analysis identified a novel orthobunyavirus, which subsequently was isolated from blood of affected animals. Surveillance was initiated to test malformed newborn animals in the affected region.