Immuno-oncology in head and neck squamous cell carcinoma - a narrative review.

Immuno-oncology studies the immune system in cancer. In recent decades, immunotherapy has shown a good response to the treatment of various locally advanced and metastatic cancers. The main mechanisms of action include stimulation of the patient's own immune system to enhance immune responses acting in tumor escape pathways. This review examined the literature related to immune system mechanisms in head and neck squamous cell carcinoma (HNSCC) and their application in immunotherapy using biomarkers. The PUBMED, LILACS, MEDLINE, WHOLIS, and SCIELO databases were searched using the terms squamous cell carcinoma, head and neck, immuno-oncology, immunotherapy, and immunology. The main drugs currently available for clinical use in patients diagnosed with HNSCC include pembrolizumab and nivolumab, both classified as check-point inhibitors. These immunobiological agents improve patient survival and quality of life. Many authors and clinical trials point out that the recommendation of these agents is linked to the dose of PD-L1 (ligand expressed primarily by tumor cells), which proved to be an unreliable biomarker in the patient selection. Recommendation of immunotherapy depends on reliable biomarkers that must be identified in order to achieve good therapeutic results.

Immuno-oncology in head and neck squamous cell carcinoma - a narrative review

Immuno-oncology studies the immune system in cancer. In recent decades, immunotherapy has shown a good response to the treatment of various locally advanced and metastatic cancers. The main mechanisms of action include stimulation of the patient's own immune system to enhance immune responses acting in tumor escape pathways. This review examined the literature related to immune system mechanisms in head and neck squamous cell carcinoma (HNSCC) and their application in immunotherapy using biomarkers. The PUBMED, LILACS, MEDLINE, WHOLIS, and SCIELO databases were searched using the terms squamous cell carcinoma, head and neck, immuno-oncology, immunotherapy, and immunology. The main drugs currently available for clinical use in patients diagnosed with HNSCC include pembrolizumab and nivolumab, both classified as check-point inhibitors. These immunobiological agents improve patient survival and quality of life. Many authors and clinical trials point out that the recommendation of these agents is linked to the dose of PD-L1 (ligand expressed primarily by tumor cells), which proved to be an unreliable biomarker in the patient selection. Recommendation of immunotherapy depends on reliable biomarkers that must be identified in order to achieve good therapeutic results.

Pain during and after-hernioplasty in raquidian or locorregional anesthesia by locking peripheral nerves.

PURPOSE: To analyze pain scores after surgery in a group of patients submitted to inguinal hernia repair under peripheral nerve block with local or spinal anesthesia. METHODS: Fifty patients were divided into two groups (both with 25 patients each). In the first group the patients were submitted to herniorrhaphy under peripheral block and local anesthesia (LG) and in the other group the patients were submitted to the same procedure under spinal anesthesia (RG). The pain was assessed using the international visual analog pain scale at four different moments. The analysis cost of the procedure was performed using the hospital's average final cost, without including medical expenses. RESULTS: The groups were homogeneous in relation to the epidemiological and clinical features. There was no significant difference between the pain in the intraoperative period and in the return visit for both groups (p = 0.17 and p = 0.18). In the immediate postoperative period, both groups reported no pain at all. In general, the RG reported a greater pain score (16% for RG and 12% for LG). Complications were more frequent in patients submitted to spinal anesthesia (40% versus 8%) (p = 0.008). The surgical time was higher in the LG (39.3 ± 9.2 min) versus (28.7 ± 7.5 min) (p = 0.01). The average final cost of the procedure was US$ 100.98 for the LG and US$ 166.19 for the RG (p = 0.00). CONCLUSION: The inguinal hernioplastia under local anesthesia plus sedation is a safe method, with a low incidence of complications, great acceptance by patients and less expensive.

Cleopatra: from turpentine and juniper to ionone and irone.

Cleopatra VII (69-30 BC), the last Ptolemaic ruler of Egypt, is probably best known for her love affairs with Julius Caesar (100-44 BC) and Marcus Antonius (83-30 BC). Rightly or wrongly she became the epitome of shrewd seduction, leading brave Roman commanders on a path to debauchery and destruction. Among the seductive strategies attributed to her is the ingestion of small amounts of turpentine [the resin of the terebinth tree (Pistacia terebinthus)] or of derived oil (Oleum terebinthinae) with the purpose of conferring to her urine a more pleasant scent reminding of violets. Turpentine components are metabolized among other compounds to ionones and irones, which - renally excreted - are responsible for the flowery scent. Having obviously worked with great generals, the strategy is said to have been embraced for everyday use by many affluent Roman women. Complicating the issue somewhat is the fact that juniper berries (Fructus juniperi) and derived oil (Oleum juniperi) containing many of the same terpenoids as turpentine have a similar effect on urine. The purpose of this contribution is to briefly review the pharmacology of turpentine and juniper derived compounds assumed to be responsible for altering the scent of urine and to examine the origin and veracity of the mentioned habit. While the effect of ingested turpentine on the scent of urine is well documented our attempts at identifying Greek or Latin authors mentioning its intentional use for this explicit purpose (by Cleopatra or anybody else) failed.

Coconut water solutions for the preservation of spleen, ovary, and skin autotransplants in rats.

BACKGROUND: The purpose of this study was to evaluate the efficacy of coconut water in the preservation of spleen, ovary, and skin autotransplantations in rats. METHODS: Fifty female Wistar rats were divided randomly into 5 groups on the basis of the following tissue graft preservation solutions: group 1, lactated Ringer's; group 2, Belzer's solution; group 3, mature coconut water; group 4, green coconut water; and group 5, modified green coconut water. In group 5, the green coconut water solution was modified to obtain the same electrolyte composition as Belzer's solution. The spleen, ovaries, and a skin fragment were removed from each animal, stored for 6 hours in one of the solutions, and then re-implanted. The recoveries of tissue functions were assessed 90 days after surgery by means of spleen scintigraphy and blood tests. The implanted tissues were collected for histological analyses. RESULTS: Higher immunoglobulin G levels were observed in the animals of group 5 than in the animals of group 1. Differences in follicle-stimulating hormone levels were observed between groups 1 and 2 (P < .001), between groups 4 and 2 (P = .03), and between groups 5 and 2 (P = .01). The spleen scintigraphy results did not differ among the groups. The ovarian tissue was better preserved in the mature coconut water group (P < .007). CONCLUSIONS: Solutions containing coconut water allowed for the preservation of the spleen, ovaries, and skin for 6 hours, and the normal functions of these tissues were maintained in rats.

Blood clearance of Howell-Jolly bodies in an experimental autogenic splenic implant model.

BACKGROUND: Autogenic splenic implant (ASI) is one of the few alternatives for preservation of splenic tissue when total splenectomy is inevitable. The aim of this study was to determine the morphological and functional regeneration of ASIs, as indicated by the clearance of Howell-Jolly (HJ) bodies, in an experimental model. METHODS: Ninety-nine male Wistar rats were divided into three groups: sham-operated (group 1), total splenectomy alone (group 2), and total splenectomy combined with ASI (group 3). Animals in group 3 were further allocated to nine subgroups of nine rats each, and analysed at different time points (1, 4, 8, 12, 16, 20, 24, 28 and 32 weeks after surgery). Blood smears were prepared at predetermined times for detection of HJ bodies. Morphological regeneration of tissue in the ASI was analysed by histology. RESULTS: At 1 week, the regenerated mass corresponded to about 7 per cent of the tissue implanted, reaching approximately 54 per cent at 24 weeks. The HJ body levels were increased in groups 2 and 3 until 8 weeks after surgery, following which levels in the ASI group became similar to those in the sham-operated group. HJ bodies were difficult to detect when a level of 22.5 per cent of regenerated ASI mass was reached. CONCLUSION: Functional regeneration of ASIs occurred from 8 weeks after surgery. When 22.5 per cent of regenerated ASI mass was reached almost no HJ bodies could be observed in the bloodstream, resembling a spleen in situ. SURGICAL RELEVANCE: Splenectomy has been practised routinely, both in the emergency setting and as a therapeutic elective procedure. There is a correlation between asplenia/hyposplenia and the occurrence of fulminant sepsis, underlining the importance of developing surgical methods for preserving splenic function. Both clinical and experimental studies have shown at least partial morphological and functional regeneration of autogenic splenic implants (ASIs). Experimental studies investigating the immunoprotective effect of ASIs, based mostly on exposure of animals to various bacteria, have demonstrated that ASIs can increase the rate of bacterial clearance and decrease mortality from sepsis. Clinical studies have shown their ability to remove colloidal substances and altered erythrocyte corpuscular inclusions, such as Howell-Jolly, Heinz and Pappenheimer bodies, from the bloodstream. In this experimental study the functional and morphological regeneration of ASIs was studied over time in rats.

Conducted healing to treat large skin wounds.

BACKGROUND: Improvement of the healing process to provide better aesthetical and functional results continues to be a surgical challenge. This study compared the treatment of skin wounds by means of conducted healing (an original method of treatment by secondary healing) and by the use of autogenous skin grafts. METHOD: Two skin segments, one on each side of the dorsum,were removed from 17 rabbits. The side that served as a graft donor site was left open as to undergo conducted healing (A)and was submitted only to debridement and local care with dressings. The skin removed from the side mentioned above was implanted as a graft (B) to cover the wound on the other side. Thus, each animal received the two types of treatment on its dorsum (A and B). The rabbits were divided into two groups according to the size of the wounds: Group 1 - A and B (4 cm2)and Group 2 - A and B (25 cm2). The healing time was 19 days for Group 1 and 35 days for Group 2. The final macro- and microscopic aspects of the healing process were analysed comparatively among all subgroups. The presence of inflammatory cells, epidermal cysts and of giant cells was evaluated. RESULTS: No macro- or microscopic differences were observed while comparing the wounds that underwent conducted healing and those in which grafting was employed, although the wounds submitted to conducted healing healed more rapidly. CONCLUSIONS: Conducted wound healing was effective for the treatment of skin wounds.

Accuracy of the new radiographic sign of fecal loading in the cecum for differential diagnosis of acute appendicitis in comparison with other inflammatory diseases of right abdomen: a prospective study.

RATIONALE: To assess the importance of the new radiographic sign of faecal loading in the cecum for the diagnosis of acute appendicitis, in comparison with other inflammatory diseases, and to verify the maintenance of this radiographic sign after surgical treatment of appendicitis. METHODS: 470 consecutive patients admitted to the hospital due to acute abdomen were prospectively studied: Group 1 [n=170]--diagnosed with acute appendicitis, subdivided into: Subgroup 1A--[n=100]--submitted to an abdominal radiographic study before surgical treatment, Subgroup 1B--[n=70]--patients who had plain abdominal X-rays done before the surgical procedure and also the following day; Group 2 [n=100]--right nephrolithiasis; Group 3 [n=100]--right acute inflammatory pelvic disease; Group 4 [n=100]--acute cholecystitis. The patients of Groups 2,3 and 4 were submitted to abdominal radiography during the pain episode. RESULTS: The sign of faecal loading in the cecum, characterized by hypo transparency interspersed with multiple small foci of hyper transparent images, was present in 97 patients of Subgroup 1A, in 68 patients of Subgroup 1B, in 19 patients of Group 2, in 12 patients of Group 3 and in 13 patients of Group 4. During the postoperative period the radiographic sign disappeared in 66 of the 68 cases that had presented with the sign. The sensitivity of the radiographic sign for acute appendicitis was 97.05% and its specificity was 85.33%. The positive predictive value for acute appendicitis was 78.94% and its negative predictive value was 98. 08%. DISCUSSION: The radiographic image of faecal loading in the cecum is associated with acute appendicitis and disappears after appendectomy. This sign is uncommon in other acute inflammatory diseases of the right side of the abdomen.

Influence of the acute alcoholism on the phagocytic function of the mononuclear phagocytic system.

RATIONALE: Alcoholics are more likely to have infections, mainly in the respiratory system. Alcohol seems to inhibit the immune system. Despite the extensive literature related to alcoholism, data related to the immune system are still not conclusive. OBJECTIVE: The purpose of this study was to verify the influence of acute alcohol intake on colloid distribution in the organs of the mononuclear phagocyte system. METHODS AND RESULTS: Thirteen male Swiss mice were divided into two groups: Group 1 (n = 5) - control, and Group 2 (n = 8) - animals that received 0.5 ml ethanol 50%, 30 minutes before the experiment. Colloidal sulphur labeled with 99mTc was used to evaluate colloid distribution in the liver, spleen and lungs. Colloid clearance was assessed as well. A gamma camera was used to measure the radioactivity of these organs and of a blood clot. No difference was found in the presence of colloid in the organs of both groups. The liver showed the highest phagocytic intake, followed by the spleen and lungs (p = 0.021 for Group 1 and p = 0.003 for Group 2). A minimum amount of radiation remained in the blood of both groups. DISCUSSION: According to the experiential conditions of this work, acute ingestion of alcohol did not interfere with the phagocytic function of the mononuclear phagocyte system in mice.

Hypoandrogenism related to early skin wound healing resistance in rats.

The purpose of this study was to verify the effect of testosterone depletion on healing of surgical skin wounds at different ages and post-operative periods. Forty-four Wistar male rats were divided into four groups: Group 1Y (n = 11) - young control, sham-operated rats (30-day old); Group 1A (n = 10) - adult control, sham-operated rats (3 to 4-month old); Group 2Y (n = 10) - young rats after bilateral orchiectomy; and Group 2A (n = 11) - adult rats after bilateral orchiectomy. After 6 months, a linear incision was performed on the dorsal region of the animals. The resistance of the wound healing was measured in a skin fragment using a tensiometer, on the 7th and 21st post-operative days. The wound healing resistance was higher in Group 1Y than in Group 2Y after 7 days (P < 0.05). Wound healing resistance at 21 days was higher than at 7 days in all groups (P < 0.05). Late wound healing resistance was not different between young and adult rats. It is concluded that bilateral orchiectomy diminished the wound healing resistance only in young animals at the 7th post-operative day.

Partial splenectomy for treatment of splenic hemangioma.

BACKGROUND: Although splenectomy is helpful in the management of splenic hemangioma, this procedure may result in a greater morbidity and even mortality, mainly caused by sepsis, when this operation is performed in children and teenagers, due to their immune deficiency. In order to avoid the adverse effects associated with the asplenism, this paper proposes partial splenectomy is proposed to treat splenic hemangioma. METHOD/CASE REPORT: A 13-year-old boy with hemangioma of the lower pole of the spleen was cared for by the authors. Partial splenectomy of the lower third part of the spleen was carried out without bleeding or technical difficulties. This patient had an uneventful postoperative follow-up. He was discharged from the hospital on the second postoperative day and returned to his normal activities after two weeks. The over twenty five-month-follow-up showed normal spleen in size and functions without clinical adverse events. CONCLUSION: Partial splenectomy should be considered and recommended as a good surgical treatment for splenic hemangioma.

Relationship between surgical trauma and albumin concentration in the postoperative period of digestive system operations.

AIM: Surgical trauma can provoke systemic alterations including changes in hepatic protein synthesis. Thus, it is important to point out the influence of this phenomenon on serum albumin concentration. The objective of the present work was to assess the effect of surgical trauma on serum albumin concentration during the immediate postoperative period in gastrointestinal procedures. METHODS: The study was conducted on 150 randomized adult patients submitted to elective major surgeries (Group 1) and to medium size surgeries (Group 2) of the gastrointestinal system, identified according to sex, age and skin color. Blood samples for the determination of serum albumin concentration were obtained on the day preceding and following the surgical procedure. RESULTS: There was a reduction in serum albumin both in Group 1 (P < 0.0001) and Group 2 (P < 0.0001), with no difference between sexes or patient skin colors for major surgeries. However, women showed a lower reduction in serum albumin than men in medium-sized surgeries. Also, the reduction of albumin was lower in black-skinned patients than in colored and lower in the latter than in white-skinned patients. With respect to age range, a greater reduction of albumin was observed in both groups among patients over 65 years, followed by younger patients (< 45 years) and by patients aged 45 to 65 years. CONCLUSION: Medium-sized and majors operations provoked an acute reduction in albuminemia, which was less intense among women, among the patients aged 45 to 65 years and among dark-skinned patients.

Efficacy of thalidomide as immunosuppressor in heterotopic heart transplantation.

BACKGROUND: Based on its anti-inflammatory and immunosuppressive effects, thalidomide has been used for the treatment of dermatologic diseases and of graft-versus-host reaction in patients submitted to bone marrow transplantation. The present study evaluated the immunosuppressive action of thalidomide alone or in combination with cyclosporine on the prevention of rejection of heterotopic cardiac allograft in rabbits. METHOD: Fifty rabbits were used, 25 of them as donors and 25 as receivers. The animals that received the graft were divided into five groups (n = 5): Group 1 (control)--non-immunosuppressed animals, Group 2 (animals immunosuppressed with cyclosporine at the dose of 10 mg/kg/day), Group 3 (animals immunosuppressed with thalidomide at the dose of 100 mg/kg/day), Group 4 (animals immunosuppressed with cyclosporine at the dose of 5.0 mg/kg/day), and Group 5 (animals immunosuppressed with cyclosporine at the dose of 5.0 mg/kg/day in combination with thalidomide at the dose of 50 mg/kg/day). The medications were administered through an orogastric catheter starting on the day before the transplant. The hearts were implanted in the abdomen and the graft vessels were anastomosed with abdominal aorta and cava. RESULTS: The combination of thalidomide and cyclosporine showed the lowest histopathological rejection score (p < 0.05). Thalidomide administered alone or in combination with cyclosporine was effective against rejection, increasing the survival (p < 0.01) of animals submitted to heterotopic heart transplantation in an abdominal position. CONCLUSIONS: Thalidomide may be considered as an adjuvant immunosuppressive drug that can be useful in transplantation.

The effect of surgical procedures on serum albumin concentration.

PURPOSE: To assess the effect of surgical trauma on serum albumin concentration during the immediate postoperative period. METHODS: 200 consecutive adult patients submitted to elective major surgeries (Group 1) and to medium size surgeries (Group 2) were identified according to gender, age and skin color. Blood samples for the determination of serum albumin concentration were obtained on the day preceding and the one following the surgical procedure. Pre- and postoperative albumin data were compared by the paired t test. The gender was compared by the Student t test. The skin color and the age were compared by the repeated measured one-way ANOVA and the Tukey-Kramer tests. The level of significance was set at P < 0.05. RESULTS: There was a reduction in serum albumin in Group 1 (p < 0.0001) and Group 2 (p < 0.0001), with no difference between gender or skin colors for major surgeries. However, women showed a lower reduction than men in serum albumin in medium-sized surgeries. In medium-sized surgeries, black patients had the lowest reduction in albuminemia. The greater reduction in albuminemia occurred in patients older than 65 years old. CONCLUSION: Medium-sized and majors operations provoked an acute reduction in albuminemia, which was more intense in aged white men.

Morphology and healing resistance of abdominal wall after longitudinal and transversal laparotomy in rabbits.

AIM: The abdominal wall continues to be a topic of investigation for the evaluation of its healing in terms of morphology and resistance. In the present investigation, transverse and longitudinal laparotomies were studied comparatively. METHODS: Thirty rabbits were divided into two groups: Group 1 (n=10) longitudinal laparotomy, Subgroup 1A (n=5) suture of the anterior and posterior sheaths of the abdominal rectus muscle and of the peritoneum, Subgroup 1B (n=5) suture of the anterior sheath of the abdominal rectus muscle; Group 2 (n=20) transverse laparotomy, Subgroup 2A (n=5) suture of the anterior and posterior sheaths of the abdominal rectus muscle and of the peritoneum, Subgroup 2B (n=5) suture of only the anterior sheath of the abdominal rectus muscle, Subgroup 2C (n=5) suture of the abdominal rectus muscle and of its anterior sheath on a single plane, Subgroup 2D (n=5) repair of the posterior sheath of the abdominal rectus muscle together with the peritoneum, followed by suture of the abdominal rectus muscle complemented with suture of the anterior sheath of the same muscle. After 17 days, two peritoneal aponeurotic muscular segments of the scar were removed for the evaluation of resistance and of histological aspects. RESULTS: The resistance values detected for each group showed 1A>1B, 1A>2A and 1B>2B, and 2B>2C>2D>2A (P=0.014). Dehiscence, infections and adhesions were more frequent in Group 2. Histology revealed muscular degeneration and necrosis, with mature fibrous connective scar tissue replacing muscle tissue. CONCLUSION: Transverse muscle section causes greater muscle weakening and leaving the peritoneum open does not alter the resistance of the scar.

Effects of immunosuppression induced by thalidomide and cyclosporine in heterotopic heart transplantation in rabbits.

UNLABELLED: Because of its anti-inflammatory and immunodepressive effects, thalidomide has been used for the treatment of dermatologic diseases and of host-versus-graft reactions in patients undergoing bone marrow transplantation. We evaluated the immunosuppressive action of thalidomide alone or in combination with cyclosporine on the prevention of rejection of heterotopic cardiac allografts in rabbits. METHODS: Fifty rabbits were used including 25 donors and 25 recipients. Recipient animals were divided into five groups (n = 5 each): group 1 (control), non-immunosuppressed animals; group II, animals immunosuppressed with cyclosporine (10 mg/kg per day); group III, immunosuppressed with thalidomide (100 mg/kg per day); group IV, immunosuppressed with cyclosporine (5.0 mg/kg per day); and group V, immunosuppressed with cyclosporine (5.0 mg/kg per day) in combination with thalidomide (50 mg/kg per day). The medications were administered through an orogastric catheter starting on the day before the transplant. The heart of the donor was implanted into the recipient's abdomen. RESULTS: The combination of thalidomide and cyclosporine showed the lowest histopathological rejection score (P < .05). Thalidomide administered alone or in combination with cyclosporine was effective against rejection, significantly increasing survival (P < .01). CONCLUSIONS: Thalidomide may be considered to be an adjuvant immunosuppressant.

Morphologic, endocrinologic and natural pregnancy assessment of intact and sliced ovarian orthotopic auto-implants in rabbits. Natural pregnancy and ovarian auto-implants.

AIM: The aim of the paper was to assess the natural pregnancy of rabbits submitted to bilateral oophorectomy and orthotopic autologous intact and sliced ovarian transplantation without a vascular pedicle and to determine the morphofunctional aspects of the reimplanted ovaries. METHODS: Thirty-two female New Zealand White rabbits were studied. The ovaries were removed and orthotopically replaced without vascular anastomosis. In Group 1 (n=8), only laparotomy and laparorrhaphy were performed. In Group 2A (n=8) intact ovaries were reimplanted on both sides. In Group 2B (n=8) both ovaries were sliced and orthotopically reimplanted. In Group 2C (n=8), an intact ovary was reimplanted on one side and a sliced ovary on the other side. Three months later, the animals were paired with sexually mature males for copulation. Estradiol, progesterone, follicle stimulating hormone and luteinizing hormone levels were assessed. A histologic study of the reimplanted ovaries, tubes and uterus was carried out, and the number of pregnancies and litters of each group were also determined. The chi squared test compared the number of successful pregnancies and the number of litters between the groups. One-way ANOVA and the Tukey-Kramer tests compared the hormonal dosages. The significance was for P <0.05. RESULTS: Pregnancies occurred in all rabbits of Group 1 between the 2(nd) and 3(rd) months after copulation, with 6 to 10 litters. In Group 2, pregnancies occurred between the 5(th) and 8(th) postoperative month. Pregnancies occurred in 37.5% of rabbits in Group 2A, and 50% in groups 2B and 2C. There was no difference in the number of litters between the reimplanted groups, with 1 to 4 litters per rabbit. Hormone levels and histology confirmed the vitality of all ovaries. CONCLUSION: Intact or sliced orthotopic autologous ovarian reimplantation without a vascular pedicle is viable in rabbits, and preserves their hormonal and fertile functions.

Arterial embolization for hemorrhage caused by hepatic arterial injury.

Fewer than 10% of patients with major liver trauma have life-threatening bleeding. Laparoscopic operations, endoscopic procedures, and percutaneous interventions such as drainages, vascular or tumor sclerosis, biopsies, and transjugular intrahepatic portocaval shunt (TIPS) have increased the number of iatrogenic vascular and bile duct injuries. Due to its therapeutic success, arterial embolization (AE) has become the standard treatment for late complications of hepatic injury. In some cases, this procedure may be used as the first approach on accidental or iatrogenic arterial trauma and in several hepatic arterial diseases. The result of this method depends on physician experience, size of the wound, and stability of the patient. Persistent hemorrhage and rebleeding may be treated with a new AE or an operation. Precise indication and a correctly performed AE are key factors for a successful treatment. Rebleeding episodes are a rare occurrence, which may be treated with AE as well.