Significant reduction of postoperative pain and opioid analgesics requirement with an Enhanced Recovery After Thoracic Surgery protocol

ObjectiveTo evaluate differences in postoperative pain control and opioids requirement in thoracic surgical patients following implementation of an Enhanced Recovery after Thoracic Surgery protocol with a comprehensive postoperative pain management strategy.Material and MethodsA retrospective analysis of a prospectively maintained database of patients undergoing pulmonary resections by robotic thoracoscopy or thoracotomy from January 1, 2017, to January 31, 2019, was conducted. Multimodal pain management strategy (opioid-sparing analgesics, infiltration of liposomal bupivacaine to intercostal spaces and surgical sites, and elimination of thoracic epidural analgesia use in thoracotomy patients) was implemented as part of Enhanced Recovery after Thoracic Surgery on February 1, 2018. Outcome metrics including patient-reported pain levels, in-hospital and postdischarge opioids use, postoperative complications, and length of stay were compared before and after protocol implementation.ResultsIn total, 310 robotic thoracoscopy and 62 thoracotomy patients met the inclusion criteria. This pain management strategy was associated with significant reduction of postoperative pain in both groups with an overall reduction of postoperative opioids requirement. Median in-hospital opioids use (morphine milligram equivalent per day) was reduced from 30 to 18.36 (P = .009) for the robotic thoracoscopy group and slightly increased from 15.48 to 21.0 (P = .27) in the thoracotomy group. More importantly, median postdischarge opioids prescribed (total morphine milligram equivalent) was significantly reduced from 480.0 to 150.0 (P < .001) and 887.5 to 150.0 (P < .001) for the thoracoscopy and thoracotomy groups, respectively. Similar short-term perioperative outcomes were observed in both groups before and following protocol implementation.ConclusionsImplementation of Enhanced Recovery after Thoracic Surgery allows safe elimination of epidural use, better pain control, and less postoperative opioids use, especially a drastic reduction of postdischarge opioid need, without adversely affecting outcomes.     

Clinicopathological and molecular characterisation of ‘multiple-classifier’ endometrial carcinomas

Endometrial carcinoma (EC) molecular classification based on four molecular subclasses identified in The Cancer Genome Atlas (TCGA) has gained relevance in recent years due to its prognostic utility and potential to predict benefit from adjuvant treatment. While most ECs can be classified based on a single classifier (POLE exonuclease domain mutations – POLEmut, MMR deficiency – MMRd, p53 abnormal – p53abn), a small but clinically relevant group of tumours harbour more than one molecular classifying feature and are referred to as ‘multiple-classifier’ ECs. We aimed to describe the clinicopathological and molecular features of multiple-classifier ECs with abnormal p53 (p53abn). Within a cohort of 3518 molecularly profiled ECs, 107 (3%) tumours displayed p53abn in addition to another classifier(s), including 64 with MMRd (MMRd–p53abn), 31 with POLEmut (POLEmut–p53abn), and 12 with all three aberrations (MMRd–POLEmut–p53abn). MMRd–p53abn ECs and POLEmut–p53abn ECs were mostly grade 3 endometrioid ECs, early stage, and frequently showed morphological features characteristic of MMRd or POLEmut ECs. 18/28 (60%) MMRd–p53abn ECs and 7/15 (46.7%) POLEmut–p53abn ECs showed subclonal p53 overexpression, suggesting that TP53 mutation was a secondary event acquired during tumour progression. Hierarchical clustering of TCGA ECs by single nucleotide variant (SNV) type and somatic copy number alterations (SCNAs) revealed that MMRd–p53abn tumours mostly clustered with single-classifier MMRd tumours (20/23) rather than single-classifier p53abn tumours (3/23), while POLEmut–p53abn tumours mostly clustered with single-classifier POLEmut tumours (12/13) and seldom with single-classifier p53abn tumours (1/13) (both p ≤ 0.001, chi-squared test). Finally, the clinical outcome of patients with MMRd–p53abn and POLEmut–p53abn ECs [stage I 5-year recurrence-free survival (RFS) of 92.2% and 94.1%, respectively] was significantly different from single-classifier p53abn EC (stage I RFS 70.8%, p = 0.024 and p = 0.050, respectively). Our results support the classification of MMRd–p53abn EC as MMRd and POLEmut–p53abn EC as POLEmut. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Acute appendicitis in the developing world is a morbid disease

IntroductionAcute appendicitis in the developing world has a markedly different disease profile to that in the developed world.MethodsA retrospective study was undertaken over a four-year period at a university hospital in South Africa to review the disease spectrum and the clinical outcome of acute appendicitis.ResultsA total of 1,004 patients (54% male, median age: 18 years) with intraoperatively confirmed appendicitis were reviewed. Over half (56%) were from the urban district within the city of Pietermaritzburg and the remaining 44% were from the rural health district. The median duration of illness from onset to definitive care was 4 days. Sixty per cent of appendices were perforated and associated with intra-abdominal contamination. Forty per cent of patients required reoperation to control intra-abdominal sepsis. Ten per cent required admission to the intensive care unit. The median overall length of hospital stay was 5 days. The mortality rate was 1%.Rural patients had a longer median duration of illness (3 vs 5 days, p<0.001) as well as a more advanced disease profile associated with perforation and severe intra-abdominal sepsis (19% vs 71%, p<0.001). Female patients had a longer median duration of illness (3 vs 4 days, p<0.001), were more likely to present with severe intra-abdominal sepsis (31% vs 54%, p<0.001) and were more likely to require a laparotomy (50% vs 73%, p<0.001). The total cost of managing the entire cohort of 1,004 patients over the 4-year period was £2,060,972.ConclusionsAcute appendicitis in South Africa is a serious disease associated with significant morbidity. Late presentation is common. Female and rural patients have the worst clinical outcomes, with significant cost to the health system.     

Subetta increases phosphorylation of insulin receptor β-subunit alone and in the presence of insulin

It has been previously shown that Subetta (a drug containing released-active forms of antibodies to the insulin receptor β-subunit and antibodies to endothelial nitric oxide synthase) stimulated insulin-induced adiponectin production by mature human adipocytes in the absence of insulin. Therefore, it was assumed that Subetta could activate the insulin receptor. To confirm this hypothesis, the capacity of Subetta to activate the insulin receptor in mature human adipocytes in the absence or presence of the insulin was investigated. Cells were incubated either with Subetta or with vehicle, or with basal medium for 3 days. Then, adipocytes were treated with water or insulin (100 nm) for 15 min. Following treatment, lysates were prepared and phosphorylation of insulin receptor β-subunits was analyzed by western blot analysis. It was shown that Subetta significantly increased (P<0.001) the ‘phosphorylated-insulin receptor β-subunit/total insulin receptor β-subunit'' ratios in both the presence and the absence of insulin. These results support previously published data and indicate that Subetta could activate the insulin receptor through the effect on its β-subunits, whose conformational state is essential for insulin receptor activation. This action might serve as one of the primary mechanisms of the drug''s antidiabetic effect.     

The utility of panoramic imaging of the temporomandibular joint in patients with temporomandibular disorders

OBJECTIVE: The objective of this study was to evaluate the utility of panoramic imaging in assessment of patients with temporomandibular disorders (TMDs). STUDY DESIGN: Fifty-five consecutive patients referred for diagnosis and management of facial pain and jaw dysfunction were included. A single examiner completed the history and clinical examination on all patients. All patients received panoramic imaging. On the basis of clinical and radiographic findings, a subset of patients received advanced imaging modalities. The panoramic radiographs were interpreted by 2 examiners; if any disagreement was noted, a third examiner interpreted the radiographs. RESULTS: Seventy-five percent of the patients had complaints of facial pain, and 75% exhibited tenderness in masticatory muscles. Tenderness was present in TM joint regions in 62%. Altered bony anatomy was seen in 43.6% of panoramic radiographs. Panoramic imaging did not lead to changes in clinical diagnosis in any of the patients seen, although the findings on the radiographs did lead to requests for additional imaging studies in 3 cases, one of which was later referred for surgical intervention because of radiographic findings. CONCLUSION: Clinical findings may be of greater relevance leading to the diagnoses associated with TMD and to determination of the need for additional imaging rather than the use of panoramic imaging in all patients with facial pain and TMD.     

Treatment of the geriatric dentally phobic patient

The elderly patient, who is phobic or exceedingly anxious established behavior patterns years ago when dentistry was not as advanced as today and when dental experiences were unpleasant and uncomfortable. The elderly phobic patient may view his role as a passive participant as he was in his youth; that is, he fears that the dentist will treat him as he was treated by an unsympathetic dentist years ago. In order to create acceptable, positive experiences for the phobic or anxious patient, the first appointment should give the patient an opportunity to know the dentist and office staff. The dentist can take this opportunity to reassure the patient that pain does not have to be a part of dental treatment. It is imperative that the dentist and staff involve the patient and instill trust. One must always have the patient's perspective in mind and constantly, by word or deed, assure the patient that he will always be in control of decisions and treatment. The dentist must not view the geriatric patient as different from his other patients. He or she must be perceptive and deliberate in the initial encounter and early relationship and determine what is the best treatment for that patient. The dentist must be realistic about the goals and requirements of that patient, for whom the dentist's ultimate objective should be to achieve quality dental care, done expeditiously, without fear and pain.     

Intralesional chemotherapy for head and neck carcinoma: a review of the literature

In the last decade chemotherapy has gained widespread acceptance in the treatment of oral and pharyngeal cancer. Current standard treatment for advanced lesions consists of concomitant radiation and chemotherapy. This approach has provided marginal improvement of prognosis for Stage III-IV disease. Recent studies have explored the idea that locally delivered cytotoxic drugs could further improve prognosis in this patient population. We review this literature with the objective of popularizing these data and suggesting future directions for treatment and clinical research for head and neck cancer.     

The utility of toluidine blue staining and brush cytology as adjuncts in clinical examination of suspicious oral mucosal lesions

The objective of this study was to investigate the utility of toluidine blue and brush cytology in patients with clinically detected oral mucosal lesions. Clinical examination of 35 patients was completed before toluidine blue application, oral brush cytology and scalpel biopsy. Lesions were photographed before and after stain application; followed by brush cytology. All findings were compared with histopathologic results. Severe dysplasia and carcinoma-in-situ were determined as ‘positive’; no dysplasia and mild to moderate dysplasia were defined as ‘negative’. The sensitivity, specificity, positive and negative predictive values of clinical examination and toluidine blue were the same: 0.923, 0.433, 0.414, and 0.929, respectively. Those of brush cytology were 0.923, 0.517, 0.462, and 0.938. The concordance of all methods was 30% for benign and 61% for malignant lesions. Adjuncts identified 92% of carcinoma-in-situ and squamous cell carcinoma as confirmed by histopathology, in contrast to clinical findings alone in which 62% of these lesions were identified (p = 0.046). In conclusion, adjunct diagnostic methods decreased the level of uncertainty for the diagnosis of oral malignancies and lichenoid dysplasias when applied as adjuncts to clinical examination.