Sunitinib-induced hypothyroidism predicts progression-free survival in metastatic renal cell carcinoma patients.

Sunitinib is a tyrosine kinase inhibitor (TKI) used in treatment of metastatic renal cell carcinoma (mRCC), gastrointestinal stromal tumors and pancreatic neuroendocrine tumors. One of the most common side effects related to sunitinib is hypothyroidism. Recent trials suggest correlation between the incidence of hypothyroidism and treatment outcome in patients treated with TKI. This study evaluates whether development of hypothyroidism is a predictive marker of progression-free survival (PFS) in patients with mRCC treated with sunitinib. Twenty-seven patients diagnosed with clear cell mRCC, after nephrectomy and in 'good' or 'intermediate' MSKCC risk prognostic group, were included in the study. All patients received sunitinib as a first-line treatment on a standard schedule (initial dose 50 mg/day, 4 weeks on, 2 weeks off). The thyroid-stimulating hormone serum levels were obtained at the baseline and every 12 weeks of treatment. In statistic analyses, we used Kaplan-Meier method for assessment of progression-free survival; for comparison of survival, we used log-rank test. In our study, the incidence of hypothyroidism was 44%. The patients who had developed hypothyroidism had better median PFS to patients with normal thyroid function 28,3 months [95% (CI) 20.4-36.2 months] versus 9.8 months (6.4-13.1 months). In survival analysis, we perceive that thyroid dysfunction is a predictive factor of a progression-free survival (PFS). In the unified group of patients, the development of hypothyroidism during treatment with sunitinib is a positive marker for PFS. During that treatment, thyroid function should be evaluated regularly.

Co-occurring adverse events enable early prediction of progression-free survival in metastatic renal cell carcinoma patients treated with sunitinib: a hypothesis-generating study.

AIMS AND BACKGROUND: Clinical practice shows significant differences in treatment outcomes and toxicity of sunitinib across patients. This retrospective study assessed early predictive markers for progression-free survival (PFS) in patients with metastatic clear cell renal cell carcinoma (RCC) treated with sunitinib in the first-line setting. METHODS: We evaluated 28 patients with stage IV clear cell RCC (with good or intermediate MSKCC risk prognosis) treated at the Department of Oncology, University Hospital, Cracow between 2008 and 2013. Data included demographic profiles, adverse events during first cycle of therapy, treatment delays, and treatment outcomes. Sunitinib was administered on a standard schedule (50 mg/day, 4 weeks on, 2 weeks off). PFS values were estimated with the Kaplan-Meier method and compared using the log-rank test; we identified independent PFS predictors using multiple Cox regression models. RESULTS: PFS was significantly longer in patients who experienced at least 1 adverse event after the first cycle of sunitinib (median 17.6 months vs. 5.6; p = 0.006). Hypertension and hand-foot syndrome were significantly correlated with longer PFS (29.3 vs. 6.0 months; p = 0.002, and not reached vs. 9.8 months; p = 0.002, respectively). We observed a similar (though not significant) tendency for neutropenia (17.5 vs. 8.4 months; p = 0.055). In multiple Cox regression, hypertension was the only individual independent predictor of PFS, but the co-occurrence of any 2 or 3 sunitinib-induced adverse events also predicted longer survival. CONCLUSIONS: Although small, our study suggests that hypertension and hand-foot syndrome predict longer PFS in patients with clear cell RCC treated with sunitinib. The co-occurrence of 2 or more side effects seems also a significant predictor of longer survival. Larger studies are warranted to confirm the correlation between co-occurring side effects and PFS.

Non-invasive assessment of the gracilis muscle by means of surface electromyography electrode arrays.

PURPOSE: The purpose of the study was the non-invasive investigation of the innervation zone (IZ) location of the gracilis muscle of both thighs by means of surface electromyography (EMG). MATERIALS AND METHODS: Multichannel EMG signals were detected by means of a flexible array of 16 equally spaced silver bar electrodes. Tests were performed on both gracilis muscles on 15 subjects. Motor unit (MU) action potentials were visually identified and extracted. The locations of the IZs of the recognized MUs were statistically analyzed to find significant differences between the subjects and between the right and left muscle of each subject. RESULTS AND CONCLUSIONS: A statistically significant difference was found between the gracilis IZ position in the two sides, with more proximal IZs on the left side. This difference suggests a possible role of surface EMG in preoperative evaluation of patients prepared for the dynamic graciloplasty procedure. This test would provide an objective criterion for the choice of the gracilis muscle to be transposed with the highest probability of success.

24-hour heart rate variability in patients with gastroesophageal reflux disease.

The GERD pathogenesis may be associated with disturbances of the autonomic nervous system (ANS), which can be revealed using heart rate variability studies (HRV). The aim of presented study was to estimate the circadian ANS activity in 24-hour HRV recordings in GERD patients, both in non-erosive form (NERD), and with erosive, inflammatory changes in the esophagus (ERD patients). Our results demonstrated disturbances in the parasympathetic ANS part, but they also delivered the proofs for possible sympathetic disorder. That is why the autonomic neuropathy in GERD patients may have mixed character.

[Current concepts of diverticular disease pathophysiology]. / Wspólczesne poglady na patofizjologifie uchylkowatosci jelita grubego.

The first description of diverticular disease (DD) is dated on XVIIIth century. During last decades the DD prevalence continuously increases, especially in western countries. Nowadays, in developed countries, DD of the left colon is one of the most common diseases of gastro-intestinal tract. Because of the prevalence and costs of treatment it is still in the limelight of scientists and medical professionals. This article summarizes basic epidemiological data and discusses actual concepts of DD pathophysiology. Despite fact DD becomes more and more important, its pathophysiology remains to be unrevealed yet. Further clinical, molecular and epidemiological studies are needed to show the process and particular stages of diverticula development and progression.

[Evaluation of intersitial cells of Cajal (ICC) in the large intestine of humans]. / Ocena komórek Cajala (ICC) w jelicie grubym u ludzi.

Interstitial Cells of Cajal (ICC) are the pacemaker cells of the smooth muscle of the gastrointestinal (GI) tract. They are binding these muscle with the enterous nervous system and play an important role in the regulation of motility of the GI tract. Disturbiud in activity of those cells were observed in many functional diseases of the GI tract. The aim of this study was to evaluate the localization and morphological differences of the ICC between some region of the human colon. In this work we have performed the immunohistochemical method, using the monoclonal and policlonal specific antibodies against c-kit receptor (CD117) in paraffin embedded block. We find the ICC in the wall of colon in the muscle layers, mainly localized in the region of the myenteric plexus. No difference of the ICC between other region of the colon were observed in our specimen. In some cases of patients with diverticulosis we have observed less of ICC according to the control group. It's only early result, but let us know, that ICC play an important role in the pathogenesis of the motility disturbances of the GI tract.

The usefulness of low-pressure pneumoperitoneum in laparoscopic surgery.

The aim of the study was to assess the usefulness of low-pressure pneumoperitoneum (LP) in laparoscopic surgery. A consecutive group of 152 patients qualified for laparoscopic cholecystectomy (LC) was assessed as to the possibility of performing the procedure with LP 7 mmHg. The following exclusion criteria were used: Body Mass Index (BMI) > 27 and laparotomy in medical history. The subsequent stage of the trial included 82 (53.9%) patients (73 females, 9 males) meeting the inclusion criteria. The mean BMI was 25.23 +/- 1.4; mean age was 46 +/- 7.8 years. All the patients suffered from symptomatic uncomplicated gallstones confirmed in ultrasound. The pneumoperitoneum was created in a blind way with a Veress needle up to pressure of 12 mmHg and the first 10 mm TERNAMIAN-EndoTip trocar was introduced under direct visual control. After the placement of other trocars, the working pressure was reduced from 12 mmHg to 7 mmHg. The pCO2 concentration was monitored intraoperatively by a capnometer. Among 82 patients included into the study the LPLC was successfully performed in 73 (89%) patients. In 8 (9.75%) patients the working pressure had to be increased to 15 mm Hg due to the gallbladder exceeding 12 cm in length and difficulties in its proper mobilization required to visualize the neck of the gallbladder. All these patients were male and 3 of them were 55 years of age or more. In 1 (1.22%) patient conversion was necessary because of difficulties in identification of anatomical structures within the Calot's triangle. LC can be performed with a use of the LP technique in the majority of patients with BMI < 27 and no previous history of laparotomy. Gallbladder assessed in preoperative ultrasound as longer than 12 cm as well as male sex and age over 55 years indicate a higher risk of failure of the 4-trocar LPLC technique.

Influence of different pressures of pneumoperitoneum on the autonomic system function during laparoscopy.

UNLABELLED: The effects of different pressure values of pneumoperitoneum on the activity of the autonomic nervous system (ANS) have not been investigated in detail. In this prospective study, 20 patients qualified for laparoscopic cholecystectomy were randomised to either low-pressure (LP = 7 mmHg) or standard-pressure (SP = 12 mmHg) pneumoperitoneum groups, 10 patients each. The anesthesia was induced with fentanyl and thiopental and maintained with isoflurane. Ventilation was mechanically controlled (18 breaths per minute, end-tidal CO2 30-35 mmHg, instant capnometer monitoring). Intraabdominal pressure was maintained automatically by a CO2 insufflator. Patient were kept in a horizontal position. The ANS was evaluated by heart rate variability (HRV) analysis (POSTER ECG 2002 System) measured intraoperatively in three recordings of 5 minutes each: in awake patient, after induction of general anesthesia, and after creation of pneumoperitoneum. Power spectral analysis of HRV was applied, the low-frequency (LF = 0.05-0.15 Hz) and high frequency (HF = 0.15-0.45 Hz) spectral density of the HRV were analysed using the Fast Fourier Transform algorithm. The appropriate statistical analysis of data was performed. LF density decreased at the anesthetized stage and increased at the insufflated stage in both groups (p < 0.01). LP resulted in lower sympathetic activation than SP pneumoperitoneum (LF: 68.12 +/- 6.56 nu vs. 78.26 +/- 5.43 nu, p < 0.01; HF: 24 +/- 2.48 nu vs. 15.56 +/- 2.54 nu, p < 0.05). IN CONCLUSION: pneumoperitoneum leads to sympathetic activation of the ANS. LP in comparison to SP pneumoperitoneum with carbon dioxide results in significantly decreased sympathetic activation during laparoscopy.