How safe is adjuvant chemotherapy and radiotherapy for rectal cancer?

Over the last three decades, a series of clinical trials have led to the use of adjuvant pelvic radiotherapy and chemotherapy in high-risk (T3-4 or N1) rectal cancer. There is a need to improve patient selection in order to identify the group most at risk for recurrent disease. The toxicity of adjuvant therapy should be factored into this consideration. The optimal sequencing of adjuvant therapy before or after surgery, the use of short- or long-course radiotherapy, and the utility of concurrent chemotherapy is currently being examined in randomized controlled trials (RCTs). The aim of this report was to review the morbidity and mortality in all RCTs of adjuvant therapy for rectal cancer.     

How important is vitamin D in preventing infections?

Interaction with the immune system is one of the most recently established nonclassic effects of vitamin D (VitD). For many years, this was considered to be limited to granulomatous diseases in which synthesis of active 1,25-dihydroxyvitamin D3 (1,25(OH)₂D₃) or calcitriol is known to be increased. However, recent reports have supported a role for 1,25(OH)₂D₃ in promoting normal function of the innate and adaptive immune systems. Crucially, these effects seem to be mediated not only by the endocrine function of circulating calcitriol but also via paracrine (i.e., refers to effects to adjacent or nearby cells) and/or intracrine activity (i.e., refers to a hormone acting inside a cell) of 1,25(OH)₂D₃ from its precursor 25(OH)D₃, the main circulating metabolite of VitD. The ability of this vitamin to influence human immune responsiveness seems to be highly dependent on the 25(OH)D₃ status of individuals and may lead to aberrant response to infection or even to autoimmunity in those who are lacking VitD. The potential health significance of this has been underlined by increasing awareness of impaired status in populations across the globe. This review will examine the current understanding of how VitD status may modulate the responsiveness of the human immune system. Furthermore, we discuss how it may play a role in host resistance to common pathogens and how effective is its supplementation for treatment or prevention of infectious diseases in humans.     

How important is urinary cytology in the diagnosis of urological malignancies?

OBJECTIVE: To audit clinical usefulness of urine cytology examination in a subspecialised urological unit setting. PATIENTS AND METHODS: Data from the hospital information support system on urinary cytology examinations carried out at one centre was audited over a period of 15 months. Source of urine cytology specimens, clinical profile of patients and the findings of urinary cytology were analysed and collated. RESULTS: A total of 1400 urinary cytology specimen on 900 patients were requested during 15 months study period. Urologists requested 1092 (78%) and non-urologists (general practitioners, physician or general surgeons) requested 318 (22%) specimens. The majority of specimens, 1115 (80%) did not show any cytological evidence of malignancy. 83 specimens (6%) showed cytological evidence of malignant cells consistent with origin from a urothelial malignancy. Among this group 87% (72) were more than 50 years of age and 60 (72%) had history of gross heamaturia. 159 (11.35) cases were reported as being suspicious of malignancy or showing atypical cells requiring further evidence. A total of 43 (3.04%) specimens were poorly preserved or insufficient for diagnosis. The positivity rate amongst urologist and non-urologists request was 56% and 6% respectively (p=0.00001 value). The source in 37 (86%) specimens reported, as poorly preserved or insufficient for diagnosis was non-urologists compared to 6 (14%) from urologists with significant p value (0.00001). CONCLUSIONS: Urinary cytology for malignant cells is a contributory investigation in the diagnosis of urological malignancy. It should be only ordered in the proper clinical situation.     

Hypoxia in head and neck cancer: How much,how important?

BACKGROUND: Hypoxia develops in tumors because of a less ordered, often chaotic, and leaky vascular supply compared with that in normal tissues. In preclinical models, hypoxia has been shown to be associated with treatment resistance and increased malignant potential. In the clinic, several reports show the presence and extent of tumor hypoxia as a negative prognostic indicator. This article reviews the biology and importance of hypoxia in head and neck cancer. METHODS: A review of literature was carried out and combined with our own experience on hypoxia measurements using exogenous and endogenous markers. RESULTS: Hypoxia can increase resistance to radiation and cytotoxic drugs and lead to malignant progression, affecting all treatment modalities, including surgery. Hypoxia measurements using electrodes, exogenous bioreductive markers, or endogenous markers show the presence of hypoxia in most head and neck cancers, and correlations with outcome, although limited, consistently indicate hypoxia as an important negative factor. Each hypoxia measurement method has disadvantages, and no "gold standard" yet exists. Distinctions among chronic, acute, and intermediate hypoxia need to be made, because their biology and relevance to treatment resistance differ. Reliable methods for measuring these different forms in the clinic are still lacking. Several methods to overcome hypoxia have been tested clinically, with radiosensitizers (nimorazole), hypoxic cytotoxins (tirapazamine), and carbogen showing some success. New treatments such as hypoxia-mediated gene therapy await proper clinical testing. CONCLUSIONS: The hypoxia problem in head and neck cancer needs to be addressed if improvements in current treatments are to be made. Increased knowledge of the molecular biology of intermediate, severe, and intermittent hypoxia is needed to assess their relevance and indicate strategies for overcoming their negative influence.     

What is new in the surgical treatment of rectal cancer?]

Rectal adenocarcinoma is a common cancer. Substantial advances in surgical technique and adjuvant treatments usually allow to preserve sphincter function, without overruling oncologic surgery standards. Sexual function is usually preserved, except in patients with locally advanced tumors. There is sound evidence that complete removal of the mesorectum and local radiation therapy decrease the rate of local recurrences. Quality of functional results after colorectal versus coloanal anastomosis is compared, and the contribution to patient comfort of construction of a reservoir is evaluated.     

Lymphadenectomy in bladder cancer: How high is “high enough”?

PURPOSE: The role of a regional lymphadenectomy in the surgical treatment of high-grade, invasive transitional cell carcinoma of the bladder has evolved over the last several decades. Although the application of a lymphadenectomy for bladder cancer is not significantly debated, the absolute extent or level of proximal dissection of the lymphadenectomy remains a controversial issue. MATERIAL AND METHODS: A review of the literature should help elucidate the rationale and extent of an appropriate lymphadenectomy in patients undergoing radical cystectomy for bladder cancer. Various surgical issues of lymphadenectomy as well as prognostic factors in patients undergoing radical cystectomy for bladder cancer are examined. RESULTS: A growing body of evidence, spanning from early autopsy and cadaveric studies to recent retrospective series and multicenter prospective trials, suggests that an extended lymph node dissection (cephalad extent to include the common iliac arteries) may provide not only prognostic information but also provide a therapeutic benefit for both patients with lymph node-positive and lymph node-negative disease undergoing radical cystectomy for bladder cancer. Although the absolute boundaries of the lymphadenectomy remain a subject of controversy, historical reports confirmed by recent lymphatic mapping studies suggest the inclusion of the common iliac as well as possibly presacral nodes in the routine lymphadenectomy for transitional cell carcinoma of the bladder. The need to extend the dissection higher to include the distal para-aortic and paracaval lymph nodes may be important in select individuals but remains more controversial. The extent of the primary bladder tumor (p-stage), number of lymph nodes removed, the lymph node tumor burden (tumor volume), and lymph node density (number of lymph nodes involved/number of lymph nodes removed) are all important prognostic variables in patients undergoing cystectomy with pathologic evidence of lymph node metastases. Systemic adjuvant chemotherapy remains a mainstay of treatment of patients with lymph node metastases. CONCLUSIONS: Radical cystectomy with an appropriately performed lymphadenectomy provides the best survival outcomes and lowest local recurrence rates. Although the absolute limits of the lymph node dissection remain to be determined, evidence supports a more extended lymphadenectomy to include the common iliac vessels and presacral lymph nodes at cystectomy in patients who are appropriate surgical candidates. When feasible, adjuvant chemotherapy is warranted in patients with positive nodal metastasis.     

How relevant is breast cancer screening in the Asia/Pacific region?

Nationwide breast cancer screening with mammography is well-established in many western countries. Many studies have shown its benefit in mortality reduction. However, breast cancer screening in Asia has been slow to implement, as it was perceived that the breast cancer incidence was low and the parenchyma of Asian women was difficult to assess mammographically. With changing disease patterns, breast cancer is now one of the most common cancers amongst women in Asia. Breast cancer screening has become an important and relevant health problem. However, apart from biological differences between western and Asian women, cultural and economic considerations need to be addressed. This paper looks at the various issues pertaining to the feasibility and relevance of population-based screening in the Asia/Pacific region.     

When is local excision appropriate for “early” rectal cancer?

Local excision is increasingly performed for “early stage” rectal cancer in the US; however, local recurrence after local excision has become a controversial issue in Western countries. Local recurrence is considered to originate based on the type of tumor and procedure performed, and in surgical margin-positive cases. This review focuses on the inclusion criteria of “early” rectal cancers for local excision from the Western and Japanese points of view. “Early” rectal cancer is defined as T1 cancer in the rectum. Only the tumor grade and depth of invasion are the “high risk” factors which can be evaluated before treatment. T1 cancers with sm1 or submucosal invasion <1,000 μm are considered to be “low risk” tumors with less than 3.2 % nodal involvement, and are considered to be candidates for local excision as the sole curative surgery. Tumors with a poor tumor grade should be excluded from local excision. Digital examination, endoscopy or proctoscopy with biopsy, a barium enema study and endorectal ultrasonography are useful for identifying “low risk” or excluding “high risk” factors preoperatively for a comprehensive diagnosis. The selection of an initial local treatment modality is also considered to be important according to the analysis of the nodal involvement rate after initial local treatment and after radical surgery.     

What is the impact of hospital and surgeon volumes on outcomes in rectal cancer surgery?

Aim

Evidence for a positive volume–outcome relationship for rectal cancer surgery is unclear. This study aims to evaluate the volume–outcome relationship for rectal cancer surgery at hospital and surgeon level in the English National Health Service (NHS).

Method

All patients undergoing a rectal cancer resection in the English NHS between 2015 and 2019 were included. Multilevel multivariable logistic regression was used to model relationships between outcomes and mean annual hospital and surgeon volumes (using a linear plus a quadratic term for volume) with adjustment for patient characteristics.

Results

A total of 13 858 patients treated in 166 hospitals were included. Six hospitals (3.6%) performed fewer than 10 rectal cancer resections per year, and 381 surgeons (45.0%) performed fewer than five such resections per year. Patients treated by high-volume surgeons had a reduced length of stay (p = 0.016). No statistically significant volume–outcome relationships were demonstrated for 90-day mortality, 30-day unplanned readmission, unplanned return to theatre, stoma at 18 months following anterior resection, positive circumferential resection margin and 2-year all-cause mortality at either hospital or surgeon level (p values > 0.05).

Conclusion

Almost half of colorectal surgeons in England do not meet national guidelines for rectal cancer surgeons to perform a minimum of five major resections annually. However, our results suggest that centralizing rectal cancer surgery with the main focus of increasing operative volume may have limited impact on NHS surgical outcomes. Therefore, quality improvement initiatives should address a wider range of evidence-based process measures, across the multidisciplinary care pathway, to enhance outcomes for patients with rectal cancer.     

Which muscarinic receptor is important in the bladder?

Antimuscarinic agents are the most widely used therapy for urge incontinence, but have side effects such as constipation, tachycardia and dry mouth, resulting from a lack of selectivity for the bladder. M₂ receptors are the predominant cholinoceptors present in urinary bladder, but mainly the minor population of M₃ receptors mediate its contraction. M₂ receptors modulate detrusor contraction by several mechanisms, and may contribute more to contraction of the bladder in pathological states such as bladder denervation or spinal cord injury. Prejunctional inhibitory M₂ or M₄ receptors and prejunctional facilitatory muscarinic M₁ receptors in the bladder have all been reported. In clinical studies, tolterodine, a non-selective muscarinic antagonist, has been reported to be as effective as oxybutynin but inducing less dry mouth. Thus, although it is not certain which antimuscarinic drugs have the better efficacy and tolerability, the non-selective antimuscarinic drugs seem to be better than M₃-selective antagonists in their clinical efficacies. However, controlled release, or intravesical, intravaginal, or rectal administrations of oxybutynin have been reported to cause fewer side effects. Darifenacin, a new M₃ selective antagonist, has been reported to have selectivity for the bladder over the salivary gland in vivo. To verify which antimuscarinic drugs selective for the muscarinic subtypes have the best efficacy and tolerability, comparative clinical trials between M₃ selective antagonists and non-selective compounds, such as olterodine, are required in the future.