👉TAX 323 Jan B. Vermorken, M.D et al. Cisplatin, Fluorouracil, and Docetaxel in Unresectable Head and Neck Cancer

👉Background

• Phase 2 studies suggest that the standard regimen of cisplatin and fluorouracil (PF) plus docetaxel (TPF):
  • Improves outcomes in squamous cell carcinoma of the head and neck.
• In the TAX 323 they compared:
  • TPF with PF as induction chemotherapy in patients with locoregionally advanced, unresectable disease.

👉Methods

• The TAX 323 randomly assigned eligible patients between the ages of 18 and 70 years who had stage III or stage IV disease and no distant metastases to:
  • Receive either TPF (docetaxel and cisplatin, day 1; fluorouracil by continuous infusion, days 1 to 5) or PF every 3 weeks for four cycles.
• Patients without progression of disease:
  • Received radiotherapy within 4 to 7 weeks after completing chemotherapy.
• The primary end point was progression free survival.

👉Results

• A total of 358 patients underwent randomization:
  • With 177 assigned to the TPF group and 181 to the PF group.
• At a median follow-up of 32.5 months.
• The median progression-free survival was:
  • 11.0 months in the TPF group
  • 8.2 months in the PF group
    • Hazard ratio for disease progression or death in the TPF group:
      • 0.72; P=0.007.
• Treatment with TPF resulted in a reduction in the risk of death:
  • Of 27% (P=0.02).
• With a median overall survival of:
  • 18.8 months in the TPF, as compared with 14.5 months in the PF group.
• There were more grade 3 or 4 events of leukopenia and neutropenia in the TPF group.
• More grade 3 or 4 events of thrombocytopenia, nausea, vomiting, stomatitis, and hearing loss in the PF group.
• The rates of death from toxic effects were:
  • 2.3% in the TPF group and 5.5% in the PF group.

👉Conclusions

• As compared with the standard regimen of cisplatin and fluorouracil, induction chemotherapy with the addition of docetaxel:
  • Significantly improved progression- free and overall survival in patients with unresectable squamous-cell carcinoma of the head and neck:
    • ClinicalTrials.gov number, NCT00003888.

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👉A paramedian mandibulotomy, avoids all the disadvantages of a lateral mandibulotomy and the sequelae of a midline mandibulotomy.

👉A paramedian mandibulotomy offers significant advantages:

• Wide exposure to the surgical field.
• Preservation of the geniohyoid and genioglossus muscles:
  • Leading to preservation of:
    • The hyomandibular complex.
• The only muscle requiring division is the mylohyoid muscle:
  • Which leads to minimal swallowing difficulties.
• A paramedian mandibulotomy does not cause denervation or devascularization of the skin of the chin or the teeth and mandible.
• Fixation at the mandibulotomy site is easy, and the site of the mandibulotomy does not fall within the lateral portal of radiation therapy if the patient needs postoperative radiotherapy:
  • Thus at present a paramedian mandibulotomy remains an optimal surgical approach for access to posteriorly located larger lesions of the oral cavity and tumors of the oropharynx and parapharyngeal space.

#Arrangoiz #Teacher #Surgeon #CancerSurgeon #HeadandNeckSurgeon #SurgicalOncologist #OralCavityCancer #PharyngealCancer

👉Nasopharyngeal carcinoma (NPC) is rare in the Western Hemisphere, showing its highest incidence in the Alaskan Eskimo and Mediterranean populations; however, it is endemic in southern China.

• The etiology of NPC is multifactorial and has:
  • Viral, genetic, and environmental factors

• Undifferentiated subtype of NPC:
  • Is strongly associated with Epstein-Barr virus (EBV):
    • EBV is also associated with earlier lesions:
      • Such as carcinoma in situ
• The nasopharynx extends anteriorly from the posterior choana of the nasal cavity to the free border of the soft palate:
  • It comprises a:
    • Vault
    • The lateral walls:
      • Including the fossa of Rosenmüller and mucosa covering the torus tubarius
    • A posterior wall
    • The superior surface of the soft palate:
      • Which is the floor
  • The posterior lip of the opening of the Eustachian tube is the torus tubarius:
    • Behind which is a mucosal fold:
      • Called the fossa of Rosenmüller

• The World Health Organization (WHO) classification for NPC encompasses:
  • Keratinizing SCC
  • Nonkeratinizing carcinomas:
    • Well differentiated
    • Undifferentiated
  • Basaloid squamous cell carcinoma

• Keratinizing SCC (type 1):
  • Is more common in North America:
    • Not associated with EBV
• Nonkeratinizing carcinoma, undifferentiated type (type 2b):
  • Is highly associated with EBV
  • Accounts for 60% of all NPCs in adults
  • The most frequent type in the pediatric population
• The first-echelon lymphatic drainage of NPC includes the :
  • Retropharyngeal lymph nodes
  • Superior jugular lymph nodes
  • Posterior cervical chain nodes

• Lymph node metastasis from NPC is common:
  • As many as 90% of patients:
    • Have evidence of unilateral nodal involvement
  • As many as 50% of patients:
    • Have evidence bilateral nodal involvement
• The nasopharynx is the upper one-third of the pharynx and is separated from the oropharynx below by the soft palate:
  • Anatomically:
    • It is the space situated behind the nasal cavities
    • Its mucosal lining starts immediately behind the posterior choana
    • It is actually located in the center of the head:
      • It is located more than 10 cm from the skin surface of the head in all directions
    • The undersurface of the body of the sphenoid bone:
      • Forms the roof (vault) of the nasopharynx:
        • Which slants downwards to form the posterior wall of the nasopharynx:
          • In front of the arch of the atlas and upper part of the body of the axis vertebrum
    • The floor of the nasopharynx:
      • Is formed by the upper surface of the soft palate:
        • Which separates the nasopharynx from the oropharynx below
      • The lateral wall of the nasopharynx is formed by:
        • The opening of the Eustachian tubes superiorly
        • The upper part of the superior pharyngeal constrictor muscle inferiorly
        • The orifice of the Eustachian (auditory tympanic) tube is delineated by:
          • An incomplete cartilaginous ring:
            • The deficient portion is in the inferolateral aspect
            • The medial portion of the cartilaginous ring:
              • Elevates the overlying mucosa to form the medial crusa:
                • Also known as the Torus tubarus
              • The slit-like space formed by this medial crusa and the posterior wall of the nasopharynx:
                • Is the fossa of Rosenmüller

• The muscular wall of the nasopharynx is formed by the:
  • Superior pharyngeal constrictors lying deep to the pharyngobasilar fascia:
    • The fascial sheets join:
      • To form a median raphe:
        • Which extends from the skull base downwards along the entire posterior pharyngeal wall
• The lymph nodes that drain the nasopharynx:
  • Lie in the retropharyngeal space:
    • Outside the pharyngobasilar fascia
    • In front of the prevertebral fascia
• The cranial nerves IX, X, XI and XII, the carotid sheath and the sympathetic trunk:
  • Traverse the parapharyngeal space:
    • Which is lateral to the superior pharyngeal constrictor
• The roof (vault) of the nasopharynx:
  • Is lined by pseudostratified ciliated epithelium
• The posterior wall of the nasopharynx:
  • Is lined with stratified squamous cells:
    • The epithelium has a well-defined basement membrane and there is abundant lymphatic tissue in the lamina propria:
      • This lymphoid tissue forms the pharyngeal tonsil or adenoid in children
• Branches of the internal maxillary artery:
  • Supply the nasopharynx
• Venous drainage is to the:
  • Pterygoid venous plexus:
    • Then to the facial and internal jugular veins
• The sensory nerve supply of the region:
  • Is from branches of the maxillary nerve (V2)
• The lymphatic supply of the nasopharynx drains into the retropharyngeal lymph nodes:
  • Efferent lymphatics from these nodes and those that come directly from the nasopharynx:
    • Drain to the deep cervical lymph nodes:
      • The lymphatic drainage then passes down the neck nodes in an orderly fashion:
        • From the high neck nodes to the lower ones

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👉Paraneoplastic syndromes (PNS) represent the clinical manifestation of the remote and indirect effects produced by tumor metabolites or other products.

👉Paraneoplastic effects are not directly mediated by tumor invasion of normal tissue, or by the disruption of normal function of the involved organ, or by distant metastases.

👉More than 260 cases of nasopharyngeal carcinoma (NPC) associated with PNS have been reported in the literature.

👉These syndromes can be divided into six main groups:

• Cutaneous or dermatologic
• Endocrine
• Hematologic
• Osteoarticular or rheumatologic
• Neurologic
• Ocular

👉The most common dermatologic / cutaneous manifestation is dermatomyositis.

👉The most common endocrinologic manifestation of PNS in NPC is syndrome of inappropriate secretion of antidiuretic hormone and occasionally Cushing’s syndrome due to ectopic ACTH production.

👉The most common hematologic manifestation of a PNS in NPC is tumor fever and leukemoid reaction.

👉The most common osteoarticular or rheumatic syndromes of PNS in NPC are clubbing of the fingers and toes.

👉The most common neurologic manifestation of PNS in NPC is sensory neuropathy and demyelinating motor polyneuropathy.

👉The most common ocular manifestation of PNS in NPC is optic neuritis.

👉PNS may occur before the NPC is manifest, or while it is in an occult stage, and thus the possibility of NPC should be considered in patients with these various disorders.

👉While some PNS will respond to direct treatment, most often the PNS subsides in parallel to response of the NPC, and thus may be useful for monitoring tumor response or recurrence.

#Arrangoiz #HeadandNeckSurgeon #CancerSurgeon #SurgicalOncologist #HeadandNeckTumors

👉Patients with small bowel carcinoids often present with a mesenteric mass without an imageable small bowel primary tumor.

• The differential diagnosis of an isolated mesenteric tumor includes:
  • Lymphoma
  • Desmoid tumor
  • Reactive lymphadenopathy:
    • From an inflammatory process
  • Mesenteric peritoneal implant:
    • From an abdominal malignancy
  • Small bowel carcinoid
• Desmoid tumors:
  • Often have a spiculated appearance on CT
• In carcinoid tumors with associated mesenteric masses:
  • The relationship to the major mesenteric vessels should be assessed:
    • As nodal carcinoid metastases:
      • Can be unresectable:
        • If they involve the root of the mesentery
• Patients with mesenteric masses should undergo:
  • Biochemical testing for carcinoid:
    • Serum chromogranin A
    • Urine 5-hydroxyindoleacetic acid [5-HIAA])
  • Endoscopy:
    • If the small bowel associated with the mesenteric mass is endoscopically accessible
  • Small bowel enterography (CT or MRI):
    • Can occasionally identify a previously occult primary small bowel tumor

Chromogranin A

• Chromogranins are peptides:
  • Released from neuroendocrine cells:
    • Vary day to day and with food intake
• Depending on the threshold used:
  • The sensitivity approaches 95%
  • The specificity is low (55%):
    • Given the high rate of false positivity:
      • As it is elevated in multiple other conditions, including:
        • Endocrine diseases
        • Inflammatory conditions
        • Proton pump inhibitor use

5-HIAA

• 5-hydroxyindoleacetic acid (5-HIAA):
  • Is the end product of serotonin metabolism:
    • It is excreted in the urine
• Twenty-four-hour urinary excretion of 5-HIAA:
  • Can be elevated:
    • In patients with carcinoid tumors
  • It is most useful in patients:
    • With carcinoid syndrome:
      • Where it has high (90%) sensitivity and specificity
  • In patients with carcinoid tumors:
    • Without carcinoid syndrome:
      • The sensitivity is lower (~ 70%) even when using a low-level 5-HIAA cutoff
• Foods containing high levels of tryptophan or serotonin and certain drugs:
  • Can result in false positive values

CT

• Small bowel carcinoid tumors:
  • Are often small (less than 2 cm median size):
    • And are thus difficult to identify by cross-sectional imaging
• Given the hypervascularity of these tumors:
  • Arterial phase:
    • May improve visibility
• More commonly:
  • CT imaging reveals:
    • Mesenteric or hepatic metastases:
      • Without a small bowel mass
• The classic CT appearance demonstrates:
  • A “spokes in a wheel” pattern:
    • With a mesenteric nodal mass (wheel)
    • With radiating desmoplastic fibrosis
  • The occult primary small bowel carcinoid tumor:
    • Is often in the bowel adjacent to the nodal metastases:
      • And may manifest with radiographic signs of:
        • A partial small bowel obstruction
• Enterography (CT or MR):
  • May have higher sensitivity in detection small bowel carcinoids:
    • But is not universally available and is understudied
  • CT imaging:
    • Often underestimates the extent:
      • Of mesenteric, peritoneal, and hepatic metastases

OctreoScan

• Indium-111 pentetreotide (OctreoScan):
  • Exploits the presence of:
    • Somatostatin receptors on carcinoid tumor cells:
      • Unlike high-grade neuroendocrine:
        • Low-grade carcinoid tumors:
          • Express:
            • High levels of somatostatin receptors
• Octreotide scans:
  • Can allow for metastatic assessment and can predict response to somatostatin analogue therapy
    • However:
      • The spatial resolution and sensitivity of small carcinoid tumor detection:
        • Is limited
• Functional PET/CT (i.e., gallium-68 dotatate) scans:
  • Offer improved sensitivity and resolution:
    • And are preferred where available

ENDOSCOPY

• Similar to small bowel adenocarcinomas:
  • Small bowel carcinoids must be in an endoscopically accessible location to be visualized by endoscopy
  • Because they are often in the distal most 60 cm of the terminal ileum:
    • Colonoscopy or retrograde enteroscopy:
      • Can often reach these tumors
• Endoscopic assessment allows opportunities to:
  • Biopsy and tattoo the lesion for identification during resection

#Arrangoiz #SurgicalOncologist #CancerSurgeon #Teacher #Surgeon #SmallBowelTumors #Carcinoids

👉While all patients with symptomatic primary hyperparathyroidism should consider surgery

• It is also indicated in the following groups of patients without symptoms:
  • Age less than 50
  • Existing renal disease:
    • GFR less than 60
  • Osteoporosis
  • Serum calcium greater than 1 mg/dL above the normal range

#Arrangoiz #ParathyroidSurgeon #ParathyroidExpert #Hyperparathyroidism

👉https://academic.oup.com/jcem/article/99/10/3595/2836348

👉Asymptomatic, small thyroid nodules (usually equal or less than 1 cm maximal diameter, 1 cm3, or 1 mL volume) confined to the thyroid and surrounded by normal thyroid parenchyma can be followed with active surveillance, with or
without cytologic confirmation, in patients who value
their normal thyroid function and who desire avoidance of thyroid surgery.

👉Patients who demonstrate tumors larger than 1.5 cm to 2.0 cm; tumors in subcapsular locations adjacent to important structures, such as the trachea and recurrent laryngeal nerve; or tumors with
documented growth rate doubling times of less than 2 years are generally considered inappropriate for observation and would be considered to have actionable disease.

👉If the tumor growth rate is unknown at the time of nodule detection, then this can be established with serial ultrasound evaluations done approximately every 6 months for 1 to 2 years.

👉The frequency of ultrasound evaluations
and long-term follow-up depends on the tumor size,
location, and established growth rate.

👉With the use of this paradigm, active surveillance continues until there is a 3-mm increase in tumor diameter (which corresponds to a 100% increase in tumor volume), identification of metastatic disease, direct invasion into surrounding structures of the thyroid, or a decision to discontinue active surveillance based on patient preference.

👉This risk-stratified, minimalistic management approach to very low-risk thyroid cancers has been shown to be safe and effective over 5 to 10 years of follow-up in studies from Japan, Korea, and the United States.

👉In the first 10 years of active surveillance follow-
up, only 2% to 8% of papillary microcarcinomas
increase equal or greater than 3 mm in maximum diameter, 12% to 14% demonstrate an increase in tumor volume of greater than 50% (the smallest change in nodule volume that can be reproducibly measured), and novel lymph node metastases
are detected in 2% to 4%.

👉The likelihood of disease progression is higher in younger patients than in older patients.

👉Importantly, at the time of disease progression, deferred surgical intervention is quite effective with excellent outcomes and no disease-specific
mortality.

#Arrangoiz #ThyroidSurgeon #ThyroidExpert #ActiveSurveillanceofThyroidCancer #HeadandNeckSurgeon #CancerSurgeon #ThyroidCancer

👉Most small bowel carcinoid tumors are asymptomatic and are discovered incidentally.

• When present, symptoms are often vague and chronic, including:
  • Abdominal pain
  • Obstructive symptoms
  • Weight loss
  • Fatigue
  • Bleeding / anemia

• Patients with small bowel carcinoids can also present with regional or distant metastases without an obvious primary tumor:
  • Most commonly manifested as a:
    • Mesenteric mass or liver metastases without an obvious small bowel tumor

• Most small bowel carcinoid tumors:
  • Secrete biologically active amines:
    • But functional hormone syndromes:
      • As seen in pancreatic neuroendocrine tumors:
        • Are rare in small bowel carcinoid tumors
  • However:
    • Patients with metastatic disease:
      • Can present with carcinoid syndrome:
        • Secretory diarrhea (80%)
        • Cutaneous flushing (60% to 85%)
        • Right heart disease (20%)
        • Wheezing and dyspnea (10% to 20%)
      • Classically, patients with carcinoid syndrome:
        • Have hepatic metastases:
          • Which bypass hepatic clearance:
            • Of serotonin
• Small bowel carcinoids:
  • Most frequently arise in the terminal ileum:
    • Often within 60 cm of the ileocecal valve

#Arrangoiz #SurgicalOncologist #CancerSurgeon #Teacher #Surgeon #SmallBowelCancer

• Individuals with colorectal adenocarcinoma are at increased risk for developing small bowel adenocarcinoma:
  • Suggesting a possible common molecular pathway
• Multiple mutations have been identified in small bowel adenocarcinomas:
  • Many of which are also implicated in colorectal cancer:
    • However:
      • The sequential genetic alterations in small bowel adenocarcinoma are less well understood than for colorectal adenocarcinoma
• Several familial syndromes:
  • Are associated with increased incidence of small bowel adenocarcinoma:
    • Hereditary cancer syndromes including:
      • Lynch syndrome (hereditary nonpolyposis colorectal cancer)
      • FAP
      • Peutz-Jeghers syndrome:
        • All of this cancer syndromes are associated with elevated lifetime rates of small bowel adenocarcinomas:
          • As high as 2% to 8%, 3% to 5% (mostly in the duodenum), and 13%, respectively

• Chronic inflammatory conditions:
  • Are also implicated in the etiology of small bowel adenocarcinoma, including:
    • Crohn disease
    • Celiac disease
      • The risk of adenocarcinoma in Crohn disease:
        • Is proportional to the extent and duration of small bowel disease:
          • With 0.2% risk at 10 years and 2.2% at 25 years
            • This is a 27- to 60-fold increased risk over the general population
    • Individuals with celiac disease:
      • Are also at 34-fold increased risk for small bowel adenocarcinoma than those without celiac disease

#Arrangoiz #CancerSurgeon #SurgicalOncologist #SmallBowelCancer #Teacher