Defining a role for systemic chemotherapy in local and advanced appendix adenocarcinoma.

BACKGROUND: Appendix adenocarcinomas (AAs) are rare tumours that often present late, with a propensity for peritoneal metastases (PMs). This study aimed to evaluate outcomes of AA patients undergoing cytoreductive surgery (CRS) with curative intent and determine the role of systemic chemotherapy. MATERIALS AND METHODS: Data were collected from a prospective database and classified according to World Health Organization (WHO) 2019 classification. Tumour clearance from CRS was described using a completeness of cytoreduction (CC) score ranging from 0 [no residual disease (RD)] to 3 (>2.5 cm RD). Patients with CC0-2 CRS received hyperthermic intraperitoneal chemotherapy (HIPEC). Systemic chemotherapy was categorised as 'prior' (>6 months before), 'neoadjuvant' (<6 months before), 'adjuvant' (<6 months after CC0-1 CRS) or 'palliative' (after CC2-3 CRS). Analyses used Kaplan-Meier and Cox regression methods. RESULTS: Between January 2005 and August 2021, 216 AA patients were identified for inclusion. Median age was 59 years (21-81 years). CRS/HIPEC was carried out in 182 (84%) patients, of whom 164/182 (76%) had mitomycin C HIPEC. CC0-1 was achieved in 172 (80%) patients. Systemic chemotherapy was given to 97 (45%) patients from the whole cohort and to 37/46 (80%) patients with positive nodes. Median overall survival (OS) was 122 months (95% confidence interval 61-182 months). After multivariate analysis, patients with acellular and lower-grade PM had similar OS to those with localised (M0) disease (P = 0.59 and P = 0.19). For patients with positive nodes, systemic chemotherapy was associated with reduced risk of death compared to no chemotherapy (P < 0.0019). CONCLUSION: This study identifies AA patients with positive lymph nodes derive the most benefit from systemic chemotherapy. We confirm the prognostic importance of stage and peritoneal grade, with excellent outcomes in patients with acellular mucin and lower-grade PM.

Long-term outcomes for patients with peritoneal acellular mucinosis secondary to low grade appendiceal mucinous neoplasms.

INTRODUCTION: Low grade appendiceal mucinous neoplasms (LAMN) are known to metastasise to the peritoneum resulting in pseudomyxoma peritonei (PMP). Literature suggests that the long-term outcome is dependent on the cellular grade of the peritoneal histology, less is known about the risk to patients with acellular mucinosis (AM) alone. This study aims to review long-term outcomes in patients with PMP treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC), whose peritoneal histology was AM secondary to LAMN. METHODS: Pathological and treatment outcomes were collected from a prospectively maintained database between 2005 and 2019. Data was collected on patients with LAMN and AM diagnosed following CRS/HIPEC. A single institution performed the surgery and pathology reporting, samples reported by three different pathologists. RESULTS: Of the 2079 patients with any appendiceal neoplasm referred between 2005 and 2019, 809 underwent CRS/HIPEC, 67 (8%) of those had PMP with purely AM secondary to a LAMN. In the AM group the median age was 59, 37 (55%) were female, follow up was for a median 39 (2-145) months. Inpatient mortality occurred in 1 patient (1.5%), disease specific mortality in 2 (3%), recurrence in 2 (3%) and disease progression in 1 (1.5%). CONCLUSION: This study has identified AM secondary to LAMN as a low risk group for recurrence following CRS/HIPEC compared with epithelial pathology. Given such a low rate of recurrence we would recommend low intensity surveillance post CRS/HIPEC. Agreed standardised pathological assessment is required to exclude cellular material in specimens and diagnose AM.

Prognostic factors for disease relapse in patients with neuroendocrine tumours who underwent curative surgery.

AIM: Surgery is the only modality of cure in patients diagnosed with neuroendocrine tumours (NETs). The aim of this study was to identify prognostic factors associated with disease relapse in patients with NETs treated by potentially-curative surgery. METHODS: Sequential patients registered in The Christie European NET Society (ENETS) Centre of Excellence, with grade (G)1 or G2 NETs who had undergone curative surgery (February 2002-June 2014) were included. Investigated prognostic factors for relapse were: age, gender, TNM stage, tumour-localisation, functionality, genetic predisposition, presence of multiple NETs, second malignancy, grade (Ki-67-based), presence of vascular and/or perineural invasion, necrosis, surgical margin (R0/R1), Eastern Cooperative Oncology Group performance status and Adult Comorbidity Evaluation co-morbidity score. RESULTS: One hundred and eighty-eight patients were identified [median age of 60 years (range 16-89)]. With a median follow-up of 2.6 years, 43 relapses occurred. The estimated median relapse-free survival (RFS) for the entire cohort was 8.0 years (95% confidence interval [CI] 5.9-10.0 years). In univariate analysis, primary NET location (p = 0.01), ENETS T-(HR-1.4; 95%-CI 1.0-2.0, p = 0.026), N-(HR-2.0, 95%-CI 1.1-3.9, p = 0.026) and M-stage (HR-2.6, 95%-CI 1.1-6.3, p = 0.052), grade (Ki-67%-based) (HR-2.5; 95%-CI 1.4-4.7; p = 0.003) and perineural invasion (HR-2.1; 95%-CI 1.1-3.9; p = 0.029) were prognostic for relapse. Factors remaining significant after multivariable analysis were tumour size (HR-1.67; 95%-CI 1.04-2.70; p = 0.03), nodal involvement (HR-2.61; 95%-CI 1.17-5.83; p = 0.013) and Ki-67 at the time of diagnosis (HR-1.93; 95%-CI 1.24-3.0; p = 0.002). CONCLUSION: Size of tumour, lymph node involvement and Ki-67 were independent prognostic factors for relapse after potentially curative surgery in NET.

Effect of thermal annealing on the thermoluminescent properties of nano-calcium fluoride and its dose-response characteristics.

Nano-CaF2, prepared by the co-precipitation method, was annealed under different annealing conditions to improve its thermoluminescence (TL) characteristics. Different annealing parameters, such as temperature (400-700°C), duration (1-4 h) and environment (vacuum and air), were explored. The effect on TL sensitivity, peak position (Tm) and full-width at half-maximum (FWHM) with respect to the different annealing conditions are discussed as they are the measure of crystallinity of the material. Annealing temperature of 500°C with annealing duration of two and a half hours in vacuum provided the highest luminescence response (i.e. maximum sensitivity, minimum peak temperature and FWHM). Wide detectable dose range (5 mGy to 2 kGy), absence of thermal quenching and sufficient activation energy (1.04 eV) of this phosphor make it suitable for dosimetric applications.

Classification of and cytoreductive surgery for low-grade appendiceal mucinous neoplasms.

BACKGROUND: Low-grade appendiceal mucinous neoplasm (LAMN) is a precursor lesion for pseudomyxoma peritonei (PMP), which, if treated suboptimally, may later disseminate throughout the abdominal cavity. The role of cytoreductive surgery for these relatively early lesions is unclear. METHODS: Clinicopathological details and treatment outcomes of patients with a LAMN and disease limited to the appendix or immediate periappendiceal tissues, referred to a national treatment centre between 2002 and 2009, were evaluated prospectively. RESULTS: Of 379 patients with a diagnosis of PMP, 43 (median age 49 years) had LAMNs localized to the appendix and periappendiceal tissue. Thirty-two patients initially presented with symptoms of acute appendicitis or right iliac fossa pain. Two distinct lesions were identified: type I (disease confined to the appendiceal lumen) and type II (mucin and/or neoplastic epithelium in the appendiceal submucosa, wall and/or periappendiceal tissue, with or without perforation). Type I lesions were managed by a watch-and-wait surveillance policy with serial measurement of tumour markers and computed tomography in 14 of 16 patients. Seventeen of 27 patients with type II lesions underwent risk-reducing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with low morbidity. After a median follow-up of 40 months, there was no disease progression in either treatment pathway. CONCLUSION: This study identified two LAMN subtypes. Type II lesions have pathological features of increased risk for dissemination and should be considered for risk-reducing cytoreductive surgery.

SEM analysis and gas permeability test to characterize polysulfone membrane prepared with polyethylene glycol as additive.

Phase inversion method is applied to prepare flat sheet asymmetric polymeric membranes from homogeneous solution of 12 wt% polysulfone (PSf) with two different solvents--N-methyl-2-pyrrolidone (NMP) and dimethyl acetamide (DMAc). 5.0 wt% polyethylene glycol (PEG) of three different molecular weight (400, 6000, and 20,000 Da) is used as the polymeric additives in the casting solution. Membranes are characterized by two different techniques viz. scanning electron microscopy (SEM) and gas permeation tests. Finally, the results of both the techniques are compared with those calculated from pure water permeation tests using Hagen-Poiseuille equation. It is found that though the values obtained from all the techniques vary from each other, their trend with increase in molecular weight of PEG seems to be the same. It is seen that when molecular weight of PEG increases from 400 to 20,000 Da, the mean pore size of the prepared membranes decreases, while the porosity and pore density show an increasing trend; the pressure normalized gas flux rises significantly and the thickness of the top layer of the prepared membrane sheet increases.

Mutational analysis of the betaglycan gene-coding region in susceptibility for ovarian failure.

BACKGROUND: Elevation of FSH is frequently a consequence of impaired ovarian follicle growth. Down-regulation of the FSH levels by inhibins is mediated through its receptor betaglycan in the gonadotrophs. Understanding of germline status of the betaglycan gene (TGFBR3) is essential for ovarian failure pathophysiology. METHODS: Sequence analysis was performed for the coding region of TGFBR3 gene in a cohort of 196 ovarian failure cases that include 133 premature ovarian failure (POF) cases, 63 primary amenorrhoea (PA) cases compared with 200 controls. RESULTS: Forty-six variants including six novel exonic variants and 16 novel intronic variants were revealed. Two variants were missense: (i) p.Iso184Val in a control and (ii) p.Pro775Ser in a POF case. Genotypic distribution of three variants (c.382-81C>T, c.382-77T>C and c.1200G>A) was significantly different in the patients as compared with the controls. Five variants c.382-81C>T, c.382-77T>C, c.566-216G>A, c.1200G>A and c.2022T>C were chosen for haplotyping. The CCAAT haplotype was significantly higher in the patient population as compared with the controls (P = 0.00007). CONCLUSION: This study establishes the first mutational report of the TGFBR3 gene in correlation with ovarian failure. Significant diversity of genotype distribution and haplotype analysis suggested susceptibility of the TGFBR3 gene for ovarian failure aetiology.

An audit of the quality of the stump and its relation to rehabilitation in lower limb amputees.

An audit was undertaken amongst the lower limb (adult) amputees, 60 unilateral transfemoral (TF) and 72 unilateral trans-tibial (TT), who attended a Disablement Services Centre (DSC) during a one year period, to determine whether amputees with better quality stumps (as assessed by a scoring system used at the Centre) achieve better outcome from prosthetic rehabilitation and whether there is any relation between the construction of the stumps and the grade of surgeons. At eighteen months (minimum follow up of six months) there were 31 (52%) TF and 54 (75%) TT amputees wearing prostheses. Some 44 amputees with Grade A stumps (score of 60 and over, out of a possible 100) needed 154 days to achieve the predicted mobility grade, 15 (34%) of them needed alteration of prosthesis, attended the Centre every 42 days and achieved the activity score of -25.7; 41 amputees with Grade B stumps (scores less than 60) needed 206 days to achieve the predicted mobility grade, 24 (58.5%) of them needed alteration of prosthesis, attended the Centre every 29 days and achieved the activity score of -39.1 (less active than Grade A). The trainee surgeons (registrars, staff grade surgeons and SHOs) produced 26 Grade A stumps out of 67 amputations (40%) and the Consultants and the Senior Registrars (senior team) produced 37 Grade A stumps out of 65 amputations (57%). However, only 36% of amputees were prescribed prostheses at their first attendance (60% Grade A, and 40% Grade B).

Study of ascitic fluid in relation to systemic and portal venous blood in hepatic cirrhosis.

Twenty uncomplicated cases of cirrhosis of liver, proved by liver biopsy, and free from other systemic diseases were studied. Glucose (pre- and postprandial) and electrolytes (Na+, K+, Cl-) values were compared to those of systemic and portal venous blood. Chloride level in ascitic fluid was found to be significantly high in cirrhosis, as compared to portal and systemic venous blood. Sodium and glucose levels were similar in ascitic fluid and portal venous blood except in two cases complicated with tuberculous peritonitis, where pre- and postprandial glucose levels were considerably low. In 55% cases, there was impaired glucose tolerance, as measured by pre- and postprandial glucose levels in systemic venous blood.

Hepatoprotective action of potentized Lycopodium clavatum L

A high potency of Lycopodium clavatum Linn (200th centesimal potency) is tested for its hepatoprotective action against carbon tetrachloride-induced hepatic damage in rat. It has been established from biochemical and histopathological studies that at least 4 doses of Lycopodium 200 can control the CCI4-induced alteration of plasma levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, acetylcholinesterase, lactate deyhydrogenase, bilirubin and urea. Protective action of the drug has also been confirmed by microanatomical studies on hepatic tissues

Effect of the extracts from Aristolochia indica Linn. on interception in female mice.

The crude petroleum ether, chloroform and alcoholic extracts from the roots of Aristolochia indica (Linn.) showed 100% interceptive activity in mature female mice at the single dose of 100 mg/kg body wt. The follow-up studies with the chloroform extract showed the most significant effect in the basic part and two acidic fractions at the single dose levels of 50 mg/kg body wt. No toxic effect was observed at the dose levels used.